Machine learning-enabled maternal risk assessment for women with pre-eclampsia (the PIERS-ML model): a modelling study.

BACKGROUND: Affecting 2-4% of pregnancies, pre-eclampsia is a leading cause of maternal death and morbidity worldwide. Using routinely available data, we aimed to develop and validate a novel machine learning-based and clinical setting-responsive time-of-disease model to rule out and rule in adverse maternal outcomes in women presenting with pre-eclampsia. METHODS: We used health system, demographic, and clinical data from the day of first assessment with pre-eclampsia to predict a Delphi-derived composite outcome of maternal mortality or severe morbidity within 2 days. Machine learning methods, multiple imputation, and ten-fold cross-validation were used to fit models on a development dataset (75% of combined published data of 8843 patients from 11 low-income, middle-income, and high-income countries). Validation was undertaken on the unseen 25%, and an additional external validation was performed in 2901 inpatient women admitted with pre-eclampsia to two hospitals in south-east England. Predictive risk accuracy was determined by area-under-the-receiver-operator characteristic (AUROC), and risk categories were data-driven and defined by negative (-LR) and positive (+LR) likelihood ratios. FINDINGS: Of 8843 participants, 590 (6·7%) developed the composite adverse maternal outcome within 2 days, 813 (9·2%) within 7 days, and 1083 (12·2%) at any time. An 18-variable random forest-based prediction model, PIERS-ML, was accurate (AUROC 0·80 [95% CI 0·76-0·84] vs the currently used logistic regression model, fullPIERS: AUROC 0·68 [0·63-0·74]) and categorised women into very low risk (-LR <0·1; eight [0·7%] of 1103 women), low risk (-LR 0·1 to 0·2; 321 [29·1%] women), moderate risk (-LR >0·2 and +LR <5·0; 676 [61·3%] women), high risk (+LR 5·0 to 10·0, 87 [7·9%] women), and very high risk (+LR >10·0; 11 [1·0%] women). Adverse maternal event rates were 0% for very low risk, 2% for low risk, 5% for moderate risk, 26% for high risk, and 91% for very high risk within 48 h. The 2901 women in the external validation dataset were accurately classified as being at very low risk (0% with outcomes), low risk (1%), moderate risk (4%), high risk (33%), or very high risk (67%). INTERPRETATION: The PIERS-ML model improves identification of women with pre-eclampsia who are at lowest and greatest risk of severe adverse maternal outcomes within 2 days of assessment, and can support provision of accurate guidance to women, their families, and their maternity care providers. FUNDING: University of Strathclyde Diversity in Data Linkage Centre for Doctoral Training, the Fetal Medicine Foundation, The Canadian Institutes of Health Research, and the Bill & Melinda Gates Foundation.

An early screening model for preeclampsia: utilizing zero-cost maternal predictors exclusively.

To provide a reliable, low-cost screening model for preeclampsia, this study developed an early screening model in a retrospective cohort (25,709 pregnancies) and validated in a validation cohort (1760 pregnancies). A data augmentation method (α-inverse weighted-GMM + RUS) was applied to a retrospective cohort before 10 machine learning models were simultaneously trained on augmented data, and the optimal model was chosen via sensitivity (at a false positive rate of 10%). The AdaBoost model, utilizing 16 predictors, was chosen as the final model, achieving a performance beyond acceptable with Area Under the Receiver Operating Characteristic Curve of 0.8008 and sensitivity of 0.5190. All predictors were derived from clinical characteristics, some of which were previously unreported (such as nausea and vomiting in pregnancy and menstrual cycle irregularity). Compared to previous studies, our model demonstrated superior performance, exhibiting at least a 50% improvement in sensitivity over checklist-based approaches, and a minimum of 28% increase over multivariable models that solely utilized maternal predictors. We validated an effective approach for preeclampsia early screening incorporating zero-cost predictors, which demonstrates superior performance in comparison to similar studies. We believe the application of the approach in combination with high performance approaches could substantially increase screening participation rate among pregnancies. Machine learning model for early preeclampsia screening, using 16 zero-cost predictors derived from clinical characteristics, was built on a 10-year Chinese cohort. The model outperforms similar research by at least 28%; validated on an independent cohort.

The role of lung and cardiac ultrasound for cardiovascular hemodynamic assessment of women with preeclampsia.

Preeclampsia remains the leading cause of maternal morbidity and mortality and is associated with abnormal body fluid homeostasis and cardiovascular dysfunction. Moreover, 2 distinct hemodynamic phenotypes have been described in preeclampsia, which might require different therapeutic approaches. Fluid restriction is mandatory in women at risk of pulmonary edema, whereas additional fluid administration may be required to correct tissue hypoperfusion in women with intravascular volume depletion. As clinical examination alone cannot discriminate among different hemodynamic patterns, optimal management of women with preeclampsia remains challenging. Noninvasive bedside ultrasound has become an important diagnostic and monitoring tool in critically ill patients, and it has been demonstrated that it can also be used in the monitoring of women with preeclampsia. Echocardiography in combination with lung ultrasound provides information on hemodynamic status, cardiac function, lung congestion, and fluid responsiveness and, therefore, could help clinicians identify women at higher risk of life-threatening complications. This review describes the cardiovascular changes in preeclampsia and provides an overview of the ultrasound methodologies that could be efficiently used for better hemodynamic assessment and management of women with preeclampsia.

Self-monitoring blood pressure in Pregnancy: Evaluation of health professional experiences of the BUMP trials.

BACKGROUND: The BUMP trials evaluated a self-monitoring of blood pressure intervention in addition to usual care, testing whether they improved detection or control of hypertension for women at risk of hypertension or with hypertension during pregnancy. This process evaluation aimed to understand healthcare professionals' perspectives and experiences of the BUMP trials of self-monitoring of blood pressure during pregnancy. METHODS: Twenty-two in-depth qualitative interviews and an online survey with 328 healthcare professionals providing care for pregnant people in the BUMP trials were carried out across five maternity units in England. RESULTS: Analysis used Normalisation Process Theory to identify factors required for successful implementation and integration into routine practice. Healthcare professionals felt self-monitoring of blood pressure did not over-medicalise pregnancy for women with, or at risk of, hypertension. Most said self-monitored readings positively affected their clinical encounters and professional roles, provided additive information on which to base decisions and enriched their relationships with pregnant people. Self-monitoring of blood pressure shifts responsibilities. Some healthcare professionals felt women having responsibility to decide on timing of monitoring and whether to act on self-monitored readings was unduly burdensome, and resulted in healthcare professionals taking additional responsibility for supporting them. CONCLUSIONS: Despite healthcare professionals' early concerns that self-monitoring of blood pressure might over-medicalise pregnancy, our analysis shows the opposite was the case when used in the care of pregnant people with, or at higher risk of, hypertension. While professionals retained ultimate clinical responsibility, they viewed self-monitoring of blood pressure as a means of sharing responsibility and empowering women to understand their bodies, to make judgements and decisions, and to contribute to their care.

First trimester screening for pre-eclampsia and targeted aspirin prophylaxis: a cost-effectiveness cohort study.

OBJECTIVE: Investigate cost-effectiveness of first trimester pre-eclampsia screening using the Fetal Medicine Foundation (FMF) algorithm and targeted aspirin prophylaxis in comparison with standard care. DESIGN: Retrospective observational study. SETTING: London tertiary hospital. POPULATION: 5957 pregnancies screened for pre-eclampsia using the National Institute for Health and Care Excellence (NICE) method. METHODS: Differences in pregnancy outcomes between those who developed pre-eclampsia, term pre-eclampsia and preterm pre-eclampsia were compared by the Kruskal-Wallis and Chi-square tests. The FMF algorithm was applied retrospectively to the cohort. A decision analytic model was used to estimate costs and outcomes for pregnancies screened using NICE and those screened using the FMF algorithm. The decision point probabilities were calculated using the included cohort. MAIN OUTCOME MEASURES: Incremental healthcare costs and QALY gained per pregnancy screened. RESULTS: Of 5957 pregnancies, 12.8% and 15.9% were screen-positive for development of pre-eclampsia using the NICE and FMF methods, respectively. Of those who were screen-positive by NICE recommendations, aspirin was not prescribed in 25%. Across the three groups, namely, pregnancies without pre-eclampsia, term pre-eclampsia and preterm pre-eclampsia there was a statistically significant trend in rates of emergency caesarean (respectively 21%, 43% and 71.4%; P < 0.001), admission to neonatal intensive care unit (NICU) (5.9%, 9.4%, 41%; P < 0.001) and length of stay in NICU. The FMF algorithm was associated with seven fewer cases of preterm pre-eclampsia, cost saving of £9.06 and QALY gain of 0.00006/pregnancy screened. CONCLUSIONS: Using a conservative approach, application of the FMF algorithm achieved clinical benefit and an economic cost saving.

Discovery and verification of extracellular microRNA biomarkers for diagnostic and prognostic assessment of preeclampsia at triage.

We report on the identification of extracellular miRNA (ex-miRNA) biomarkers for early diagnosis and prognosis of preeclampsia (PE). Small RNA sequencing of maternal serum prospectively collected from participants undergoing evaluation for suspected PE revealed distinct patterns of ex-miRNA expression among different categories of hypertensive disorders in pregnancy. Applying an iterative machine learning method identified three bivariate miRNA biomarkers (miR-522-3p/miR-4732-5p, miR-516a-5p/miR-144-3p, and miR-27b-3p/let-7b-5p) that, when applied serially, distinguished between PE cases of different severity and differentiated cases from controls with a sensitivity of 93%, specificity of 79%, positive predictive value (PPV) of 55%, and negative predictive value (NPV) of 89%. In a small independent validation cohort, these ex-miRNA biomarkers had a sensitivity of 91% and specificity of 57%. Combining these ex-miRNA biomarkers with the established sFlt1:PlGF protein biomarker ratio performed better than either set of biomarkers alone (sensitivity of 89.4%, specificity of 91.3%, PPV of 95.5%, and NPV of 80.8%).

Leveraging quality improvement to promote health equity: standardization of prenatal aspirin recommendations.

OBJECTIVE: Aspirin (ASA) is recommended for patients at elevated risk of preeclampsia. Limited data exists on adherence to guidelines for ASA prescription. This project evaluates the implementation of a standardized approach to ASA prescription in an academic OB/Gyn practice. METHODS: We implemented a quality improvement project to evaluate compliance with the United States Preventative Services Task Force (USPSTF) recommendations for ASA to prevent preeclampsia. Pre-intervention, we analyzed prescription adherence at 201 New Obstetric (NOB) visits. A multi-step intervention was then implemented at 199 NOB visits. Nurses utilized a checklist created from USPSTF guidelines to identify high-risk patients, defined as having ≥1 high-risk factor or ≥2 moderate-risk factors. ASA orders were placed by physicians. A Plan-Do-Study-Act (PDSA) cycle was performed, and changes implemented. Primary outcome was percent of patients screened at RN intake visit (goal = 90%). Secondary outcomes were percent of patients who screened positive that received the ASA recommendation (goal = 80%) and percent screened and recommended by race. RESULTS: Pre-intervention, 47% of patients met criteria for ASA and 28% received a documented recommendation. Post-intervention, 99% were screened. Half (48%) met criteria for an ASA recommendation and 79% received a recommendation (p = < 0.001). Rates of appropriate recommendation did not differ by Black (80%) vs. non-Black (79%) status (p = 0.25). Subsequent PDSA cycles for 12 months neared 100% RN screening rates. Physicians correctly recommended ASA 80-100% of the time. CONCLUSION: It is feasible, sustainable and equitable to standardize screening and implementation of ASA to patients at high risk for preeclampsia. Providers can easily reproduce our processes to improve delivery of equitable and reliable preventative obstetric care.

First-Trimester Screening Program for the Risk of Pre-eclampsia Using a Multiple-Marker Algorithm: A Health Technology Assessment.

Background: Pre-eclampsia is when high blood pressure develops after 20 weeks of pregnancy and either proteinuria, maternal end-organ dysfunction, or uteroplacental dysfunction causing fetal growth restriction also develops. The Fetal Medicine Foundation has created an algorithm ("the FMF algorithm") that uses maternal factors in combination with biophysical and biochemical markers to identify people at high risk for pre-eclampsia so that they can been offered acetylsalicylic acid (Aspirin) as a preventive measure. We conducted a health technology assessment to evaluate the safety, effectiveness, and cost-effectiveness of a first-trimester population-wide screening program for pre-eclampsia risk that uses the FMF algorithm ("the FMF-based screening program"). We also evaluated the accuracy of the FMF algorithm, the budget impact of publicly funding the population-wide FMF-based screening program, and patient preferences and values. Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each study using the Risk of Bias in Non-randomized Studies-of Interventions tool and the Quality Assessment of Diagnostic Accuracy Studies-Comparative tool, and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted a cost-effectiveness analysis comparing the FMF-based screening program to standard care (screening for risk of pre-eclampsia using maternal factors alone) from a public payer perspective. We also analyzed the budget impact of publicly funding a population-wide FMF-based screening program in Ontario. We spoke with people who have experience with pregnancy and preeclampsia and their family members through direct interviews to gather preferences and values surrounding pre-eclampsia and the potential screening program. Results: We included nine studies in the clinical evidence review. The FMF-based screening program likely reduces the risk of pre-eclampsia with delivery at less than 37 weeks' gestation compared with standard care, when initiated at 11+0 to 13+6 weeks' gestation; risk ratios ranged from 0.64 (95% confidence interval [CI] 0.46-0.93) to 0.70 (95% CI 0.58-0.84) (GRADE: Moderate). It may reduce the risks of low birth weight (risk ratio 0.89 [95% CI 0.85-0.94]) and low Apgar score (risk ratio 0.73 [95% CI 0.63-0.85]) (GRADE: Low). Evidence on the effectiveness of the FMF-based screening program in reducing the risk of stillbirth and neonatal death was highly uncertain (GRADE: Very low). In addition, the FMF algorithm can improve the detection rate of pre-eclampsia with delivery at less than 37 weeks' gestation or at less than 34 weeks' gestation compared with conventional algorithms, although there are concerns about bias and applicability across studies. The population-wide FMF-based screening program is more effective and more costly than standard care. The incremental cost-effectiveness ratio of the population-wide FMF-based screening program compared with standard care is $3,446 per prevented case of pre-eclampsia with delivery at less than 37 weeks. The annual budget impact of publicly funding the population-wide FMF-based screening program in Ontario ranges from an additional $1.23 million in year 1 to $3.56 million in year 5, for a total of $8.50 million over the next 5 years. The population-wide FMF-based screening program was seen as valuable by those who have experienced pregnancy and their family members. Strong emphasis was placed on providing education and equitable access as part of any screening program, and participants valued the potential clinical benefits that the population-wide FMF-based screening program could provide. Conclusions: The FMF-based screening program is likely more effective than standard care in reducing the risk of pre-eclampsia with delivery at less than 37 weeks' gestation. Also, the FMF algorithm can improve the detection rate of pre-eclampsia with delivery at less than 37 weeks' gestation or at less than 34 weeks' gestation when compared with conventional algorithms. The population-wide FMF-based screening program is more effective and more costly than standard care. We estimate that publicly funding the population-wide FMF-based screening program in Ontario would result in additional costs of $8.50 million over the next 5 years. Pregnant people and their family members valued the potential equitable access, information, and clinical benefits that the population-wide FMF-based screening program could provide.

Cost-effectiveness analysis of a first-trimester screening test for preterm preeclampsia in the Netherlands.

OBJECTIVES: The risk of preterm preeclampsia (PT PE) can significantly be reduced by starting acetylsalicylic acid ≤ 16 weeks of gestational age. First trimester predictive models based on maternal risk factors to effectively start this therapy lacked sufficient power, but recent studies showed that these models can be improved by including test results of biochemical and/or -physical markers. To investigate whether testing a biochemical marker in the first trimester is cost-effective in the Netherlands, a cost-effectiveness analysis was performed in this study. STUDY DESIGN: The outcome of this study was expressed as an incremental cost-effectiveness ratio (ICER) with as effect prevented PT PE cases. To evaluate the impact of each model parameter and to determine model uncertainties, both univariate and probabilistic sensitivity analyses were performed. RESULTS: When compared to the baseline strategy, the test strategy is estimated to save almost 4 million euros per year on a national scale and at the same time this would prevent an additional 228 PT PE cases. The sensitivity analyses showed that the major drivers of the result are the costs to monitor a high-risk pregnancy and the specificity and that most of the model simulations were in the southeast quadrant: cost saving and more prevented complications. CONCLUSIONS: This study showed that a first-trimester test strategy to screen for PT PE in the first trimester is potentially cost-effective in the Dutch healthcare setting. The fact that the specificity is a major driver of the ICER indicates the importance for a (new) screening model to correctly classify low-risk pregnancies.

Placental Growth Factor (PlGF)- Based Biomarker Testing to Help Diagnose Pre-eclampsia in People With Suspected Pre-eclampsia: A Health Technology Assessment.

Background: Pre-eclampsia is a potentially serious condition affecting up to 5% of pregnancies, most frequently after 20 weeks' gestation. Placental growth factor (PlGF)-based tests measure either the blood level of PlGF or the ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to PlGF. They are intended to complement standard clinical assessment to help diagnose pre-eclampsia in people with suspected pre-eclampsia. We conducted a health technology assessment of PlGF-based biomarker testing as an adjunct to standard clinical assessment to help diagnose pre-eclampsia in pregnant people with suspected pre-eclampsia, which included an evaluation of diagnostic accuracy, clinical utility, cost-effectiveness, the budget impact of publicly funding PlGF-based biomarker testing, and an assessment of preferences and values. Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using AMSTAR 2, Cochrane Risk of Bias tool, the Quality of Diagnostic Accuracy Studies 2 (QUADAS-2) tool, and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic literature search of the economic evidence. We did not conduct a primary economic evaluation as the impact of the test on maternal and neonatal outcomes is uncertain. We also analyzed the budget impact of publicly funding PlGF-based biomarker testing in pregnant people with suspected pre-eclampsia in Ontario. To contextualize the potential value of PlGF-based biomarker testing, we spoke with people whose pregnancies had been impacted by pre-eclampsia as well as their family members. Results: We included one systematic review and one diagnostic accuracy study in the clinical evidence review. The Elecsys sFlt-1/PlGF ratio test using a test cut-off of less than 38 for ruling out pre-eclampsia within 1 week yielded a negative predictive value (NPV) of 99.2% and the DELFIA Xpress PlGF 1-2-3 test using a cut-off of 150 pg/mL or greater for ruling out pre-eclampsia within 1 week yielded a NPV of 94.8% (diagnostic GRADE: Moderate for both tests). All clinical utility outcomes were associated with uncertainties (GRADE: Low).We included 13 studies in the economic evidence review, most of which concluded that the use of PlGF-based biomarker testing resulted in cost savings. Seven studies were partially applicable to the Ontario health care setting but have some important limitations; the remaining 6 studies were not applicable. We estimated that publicly funding PlGF-based biomarker testing for people with suspected pre-eclampsia in Ontario would lead to an additional annual cost of $0.27 million in year 1 to $0.46 million in year 5, for a total additional cost of $1.83 million over 5 years.Direct engagement included 24 people who had been impacted by pre-eclampsia during their pregnancies as well as one family member. Participants described the emotional and physical impacts of having suspected pre-eclampsia and subsequent treatments. Those that we spoke with valued shared decision-making and identified potential gaps in patient education, specifically as it relates to symptom management for suspected pre-eclampsia. Overall, the participants viewed PlGF-based biomarker testing positively for its perceived medical benefits and minimal invasiveness. They felt that access to PlGF-based biomarker testing may also improve health outcomes through improved patient education, care coordination, and patient-centred care (e.g., prompting more frequent prenatal monitoring, when needed). In addition, PlGF-based biomarker testing was perceived to be equally beneficial for family members who may act as the health care proxy in an emergency. Lastly, participants emphasized that there should be equitable access to PlGF-based biomarker testing and support from a care provider should be offered when trying to interpret the results, particularly if the results are accessible through an online patient portal. Conclusions: Compared with standard clinical assessment alone in people with suspected pre-eclampsia (gestational age between 20 and 36 weeks + 6 days), PlGF-based biomarker testing as an adjunct to standard clinical assessment likely improves prediction of pre-eclampsia. It may also reduce time to pre-eclampsia diagnosis, severe adverse maternal outcomes, and length of stay in the neonatal intensive care unit, although the evidence is uncertain. PlGF-based biomarker testing may result in little to no difference in other clinical outcomes such as maternal admission to hospital and perinatal adverse outcomes.The economic literature review showed that PlGF-based biomarker testing was cost-effective for use in people with suspected pre-eclampsia, but with some uncertainties. A primary economic evaluation was not done for this health technology assessment because the impact of the test on maternal and neonatal outcomes is uncertain. Publicly funding PlGF-based biomarker testing for people with suspected pre-eclampsia would lead to an additional cost of $1.83 million over 5 years.Publicly funding PlGF-based biomarker testing was viewed favourably by people directly impacted by pre-eclampsia as well as their family members. Those with whom we spoke valued testing to help diagnose suspected pre-eclampsia and valued the potential medical benefits. Participants emphasized that patient education, and equitable access to PlGF-based biomarker testing should be requirements for implementation in Ontario.

Assessment of CA-125 First-Trimester Values as a Potential Screening Marker for Pre-Eclampsia.

Background: Pre-eclampsia is a major public health issue. Current screening methods are based on maternal characteristics and medical history, but complex predictive models combining different clinical and biochemical markers have been proposed. However, although their accuracy is high, the implementation of these models in clinical practice is not always feasible, especially in low- and middle-resource settings. CA-125 is a tumoral marker, accessible and cheap, with proven potential as a severity marker in the third trimester of pregnancy in pre-eclamptic women. Assessment of its use as a first-trimester marker is necessary. Methods: This observational study involved fifty pregnant women between 11 and 14 weeks of pregnancy. Clinical and biochemical markers (PAPP-A), known for their value in pre-eclampsia screening, were recorded for every patient as well as first-trimester value of CA-125 and third-trimester data regarding blood pressure and pregnancy outcome. Results: No statistical correlation between CA-125 and first-trimester markers was observed except with PAPP-A, with which it exhibited a positive correlation. Additionally, no correlation was made between it and third-trimester blood pressure or pregnancy outcomes. Conclusions: CA-125 first-trimester values do not represent a valuable marker for pre-eclampsia screening. Further research on identifying an accessible and cheap marker to improve pre-eclampsia screening in low- and middle-income settings is needed.

Which first-trimester risk assessment method for preeclampsia is most suitable? A model-based impact study.

BACKGROUND: Low-dose aspirin treatment reduces the risk of preeclampsia among high-risk pregnant women. Internationally, several first-trimester risk-calculation methods are applied. OBJECTIVE: This study aimed to assess the costs and benefits of different first-trimester preeclampsia risk estimation algorithms: EXPECT (an algorithmic prediction model based on maternal characteristics), National Institute for Health and Care Excellence (a checklist of risk factors), and the Fetal Medicine Foundation (a prediction model using additional uterine artery Doppler measurement and laboratory testing) models, coupled with low-dose aspirin treatment, in comparison with no risk assessment. STUDY DESIGN: We constructed a decision analytical model estimating the number of cases of preeclampsia with each strategy and the costs of risk assessment for preeclampsia and early aspirin treatment, expressed in euros (€) in a hypothetical population of 100,000 women. We performed 1-way sensitivity analyses to assess the impact of adherence rates on model outcomes. RESULTS: Application of the EXPECT, National Institute for Health and Care Excellence, and Fetal Medicine Foundation models results in respectively 1.98%, 2.55%, and 1.90% of the women developing preeclampsia, as opposed to 3.00% of women in the case of no risk assessment. Overall, the net financial benefits of the EXPECT, National Institute for Health and Care Excellence, and Fetal Medicine Foundation models relative to no risk assessment are €144, €43, and €38 per patient, respectively. The respective percentages of women receiving aspirin treatment are 18.6%, 10.2%, and 6.0% for the 3 risk assessment methods. CONCLUSION: The EXPECT and Fetal Medicine Foundation model are comparable with regard to numbers of prevented preeclampsia cases, and both are superior to the National Institute for Health and Care Excellence model and to no risk assessment. EXPECT is less resource-demanding and results in the highest cost savings, but also requires the highest number of women to be treated with aspirin. When deciding which strategy is preferable, cost savings and easier use have to be weighed against the degree of overtreatment, although low-dose aspirin has no clear disadvantages during pregnancy.

The prediction of hypertensive disorders by maternal hemodynamic assessment in the first trimester of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy and fetal growth restriction share common etiopathological origins and could be caused by maternal hemodynamic maladaptation to pregnancy. OBJECTIVE: The aim of our study is to evaluate if there is a correlation between maternal hemodynamic detected by UltraSonic Cardiac Output Monitor (USCOM®) during the first trimester and the pregnancy outcome. STUDY DESIGN: We recruited a nonconsecutive series of women in the first trimester of pregnancy with no previous history of hypertensive disorders. We measured the pulsatility index uterine arteries and performed a hemodynamic evaluation by USCOM® device. After delivery, we reported the development of hypertensive disorders or intrauterine fetal growth restriction later during gestation. RESULTS: A total of 187 women were enrolled during the first trimester; 17 (9%) developed gestational hypertension or preeclampsia while 11 (6%) delivered a restricted growth fetus. Mean uterine artery pulsatility index above the 95th percentile was significantly more frequent in both women who developed hypertension and those with fetal growth restriction compared to controls. Hemodynamic parameters (reduced cardiac output and increased total vascular resistance) were significantly different in the group that developed hypertensive disorders, compared to uncomplicated pregnancy. ROC curves demonstrated the usefulness of uterine artery pulsatility index in the prediction of fetal growth restriction, while hemodynamic parameters were significantly associated to the development of hypertensive disorders. CONCLUSIONS: Hemodynamic maladaptation to pregnancy may predispose to the development of hypertension, while we demonstrated a significative relationship between growth restriction and mean uterine pulsatility index. Further studies are needed to assess the value of hemodynamics evaluation in screening protocols of preeclampsia.

Assessment of maternal serum SERPINC1, E-selectin, P-selectin, and RBP4 levels in pregnancies with early- and late-onset preeclampsia.

INTRODUCTION: To investigate whether the SERPINC1, E-selectin, P-selectin, and RBP4 levels in first trimester maternal serum was associated with the presence of preeclampsia (PE). METHODS: This cross-sectional study was conducted on 26 women with early-onset preeclampsia (EO-PE), 27 women with late-onset preeclampsia (LO-PE), and 27 women with uncomplicated pregnancies. Levels of serum SERPINC1, E-selectin, P-selectin, and RBP4 were measured with the use of an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: E-Selectin levels in patients with EO-PE were higher than those with LO-PE and control patients (pE-L  = 0.025; pE-C  = 0.000; p < 0.05). There was no significant intergroup difference in terms of P-selectin and RBP4 levels (p > 0.05). SERPINC1 levels were lower in the patients in the with EO-PE group than in those in the LO-PE and the control groups (pE-L  = 0.000; pE-C  = 0.000; p < 0.05). In the PE group, there was a negative, moderate (41.7%) correlation between E-selectin level and SERPINC1 (p = 0.002; p < 0.05). The receiver operating characteristic (ROC) curve showed that the best cut-off values for E-selectin were 23.14 ng/ml > with 100% sensitivity and 100% specificity. The ROC curve showed that the best cut-off values for SERPINC1 were ≤87.76 ng/ml with 98.1% sensitivity and 96.3% specificity. DISCUSSION: Of the endothelial damage parameters, E-selectin and SERPINC1 are especially associated with EO-PE. Furthermore, they can be used as potential early diagnosis markers in the prediction of PE.

Economic Impact Analysis of Incorporation of Elecsys sFlt-1/PlGF Ratio Into Routine Practice for the Diagnosis and Follow-Up of Pregnant Women With Suspected Preeclampsia in Argentina.

OBJECTIVES: Preeclampsia (PE) is a hypertensive disorder of pregnancy that can cause severe complications and adverse fetal/maternal outcomes. We aimed to estimate the annual economic impact of incorporating Elecsys® sFlt-1/PlGF PE ratio, which measures soluble fms-like tyrosine kinase-1 and placental growth factor, into routine clinical practice in Argentina to aid diagnosis of PE and hemolysis, elevated liver enzymes, and low platelets syndrome from second trimester onward in pregnancies with clinical suspicion of PE. METHODS: A decision tree was used to estimate annual economic impact on the Argentine health system as a whole, including relevant costs associated with diagnosis, follow-up, and treatment from initial presentation of clinically suspected PE to delivery. Annual costs of a standard-of-care scenario and a scenario including PE ratio (reference year 2021) were analyzed. RESULTS: The economic model estimated that using the sFlt-1/PlGF ratio would enable the overall health system to save ∼$6987 million Argentine pesos annually (95% confidence interval $12 045-$2952 million), a 39.1% reduction in costs versus standard of care, mainly due to reduced hospitalizations of women with suspected PE. The economic impact calculation estimated net annual savings of approximately $80 504 Argentine pesos per patient with suspected PE. Based on the assumed uncertainty of the parameters, the likelihood the intervention would be cost saving was 100% for the considered scenarios. CONCLUSION: Our analysis suggests that the implementation of the sFlt-1/PlGF ratio in women with suspected PE in Argentina will enable the health system to achieve significant savings, contributing to more efficient clinical management through the likely reduction of unnecessary hospitalizations, depending on assumptions. Results rest on the payers' ability to recover savings generated by the intervention.

Platelet Indices and Erythrocyte Sedimentation Rate are useful Parameters in the Assessment of a Cohort of Nigerian Women with Preeclampsia.

BACKGROUND: The study compared some haematological parameters in normotensive pregnant women with those of women with pre-eclampsia (PE) to identify those parameters that may reinforce the occurrence and severity of PE. METHODS: The study was a case-control study involving 40 pre-eclamptic women as subjects and 40 normotensive pregnant women as controls. The subjects were classified into mild and severe based on their blood pressure of >140/90 mmHg and >169/100 mmHg, respectively. Full blood count (FBC) was done using a haematology autoanalyzer, D-dimer and fibrinogen were assessed by enzyme-linked immunosorbent assay (ELISA) method, while Prothrombin Time (PT) and activated plasma thromboplastin time (aPTT) were done manually. RESULTS: The mean PCV was higher while the mean WBC was lower in PE but the differences were not statistically significant. The ESR was significantly higher (50.48 ± 2.90mm/hr vs 41.05 ± 3.74mm/hr, p < 0.049). The mean neutrophil (59.38 ± 7.77% vs 64.95 ± 6.68%; p < 0.001) and lymphocyte (31.35±7.67% vs 7.63±7.47%, p = 0.031) counts were significantly lower and higher, respectively, in PE. Although the mean platelet count in PE was lower, the plateletcrit, mean platelet volume (MPV), and platelet distribution width (PDW) were significantly higher in PE (p = 0.01, 0.04, 0.001, respectively). The D-dimer was significantly higher in the women with PE (p < 0.001), while the PT, aPTT and fibrinogen concentrations were not statistically different between the two groups. CONCLUSION: It may be concluded that low platelet count, high MPV, PDW, PCT and ESR in PE women may reinforce the diagnosis while a high MPV may, in addition, discriminate between severe and mild Pre-eclampsia.

CONTEXTE: L'étude a comparé certains paramètres hématologiques chez des femmes enceintes normotendues à ceux de femmes atteintes de pré-éclampsie (PE) afin d'identifier les paramètres qui peuvent renforcer l'occurrence et la gravité de la PE. MÉTHODES: Il s'agissait d'une étude cas-témoins impliquant 40 femmes pré-éclamptiques comme sujets et 40 femmes enceintes normotendues comme témoins. Les sujets ont été classés en légers et sévères sur la base de leur pression artérielle de > 140/90 mmHg et >169/100 mmHg respectivement. La formule sanguine complète (FBC) a été réalisée à l'aide d'un auto-analyseur d'hématologie, les D-dimères et le fibrinogène ont été évalués par la méthode ELISA (enzymelinked immunosorbent assay), tandis que le temps de prothrombine (PT) et le temps de thromboplastine plasmatique activé (aPTT) ont été réalisés manuellement. RÉSULTATS: Le VPC moyen était plus élevé tandis que le nombre moyen de globules blancs était plus faible dans l'EP, mais les différences n'étaient pas statistiquement significatives. L'ESR était significativement plus élevé (50.48 ± 2.90mm/hr vs 41.05 ± 3.74mm/hr, p < 0.049). Les numérations moyennes des neutrophiles (59,38 ±7,77 % contre 64,95 ± 6,68 % ; p < 0,001) et des lymphocytes (31,35±7,67 % contre 27,63±7,47 %, p = 0,031) étaient respectivement plus faibles et plus élevées de manière statistiquement significative dans l'EP. Bien que la numération plaquettaire moyenne dans l'EP soit plus faible, le critère plaquettaire, le volume plaquettaire moyen (VPM) et la largeur de distribution plaquettaire (LDP) étaient significativement plus élevés dans l'EP (p = 0,01, 0,04, 0,001 respectivement). Le D-dimère était significativement plus élevé chez les femmes atteintes d'EP (p < 0,001), tandis que les concentrations de PT, aPTT et fibrinogène n'étaient pas statistiquement différentes entre les deux groupes. CONCLUSION: On peut conclure qu'une faible numération plaquettaire, un VPM élevé, un PDW, un PCT et un ESR chez les femmes atteintes d'EP peuvent renforcer le diagnostic, tandis qu'un VPM élevé peut, en outre, faire la distinction entre une pré-éclampsie grave et une pré-éclampsie légère. Mots clés: Prééclampsie, Numération plaquettaire, Indices plaquettaires, ESR, D-Dimères, Gravité.

[MATERNAL SERUM ANGIOGENIC FACTORS AS AN AIDING TOOL FOR SCREENING WOMEN WITH SUSPECTED PREECLAMPSIA NEAR DELIVERY - INITIAL DATA AND AN ESTIMATED COST-BENEFIT].

INTRODUCTION: Preeclampsia (PE) is a major pregnancy complication, posing considerable morbidity and mortality. The maternal serum angiogenic factors - PlGF and sFlt-1, and their ratio appear to be promising markers to predict PE. Aims: To assess whether the evaluation of PlGF and sFlt-1 adds to the clinical workup of women with suspected PE, and to estimate the cost/benefit. METHODS: We prospectively enrolled pregnant women with suspected PE who were admitted to the Maternal-Fetal Medicine Unit (MFM) at Shamir Medical Center. Pregnancy and delivery records were collected from their computerized electronic medical records. PlGF<150pg/ml and sFlt-1/PlGF>38 measured prospectively were used to predict PE. RESULTS: Of 105 women included, 28 were in the control group with unrelated complications and none developed PE. Among 66 women with suspected PE, 27(41%) developed the syndrome, with a positive predictive value (PPV) of 90.3% for PlGF<150 pg/ml and 88.9% for sFlt-1/PlGFabove 38. Out of 11 women with suspected intrauterine growth restriction (IUGR), six developed the syndrome, and among them, the negative predictive value (NPV) was ~ 90%. CONCLUSIONS: Angiogenic factors are reliable in predicting PE near delivery. Of 8355 annual deliveries, 584 were admitted for suspected PE. The annual test cost was NIS 66,576 (NIS 140 per single test). Cost-saving was NIS 2.18 million, the ratio of cost saved vs. test cost was 32.7. DISCUSSION: The angiogenic factors are efficient and cost-saving in PE prediction near delivery. A larger study is necessary to determine the inclusion of angiogenic factors in the workup for suspected PE.

Clinical value and cost analysis of the sFlt-1/PlGF ratio in addition to the spot urine protein/creatinine ratio in women with suspected pre-eclampsia: PREPARE cohort study.

BACKGROUND: This study investigated the clinical value of adding the sFlt-1/PlGF ratio to the spot urine protein/creatinine ratio (PCr) in women with suspected pre-eclampsia. METHODS: This was a prospective cohort study performed in a tertiary referral centre. Based on the combination of PCr (< 30) and sFlt-1/PlGF (≤38) results, four groups were described: a double negative result, group A-/-; a negative PCr and positive sFlt-1/PlGF, group B-/+; a positive PCr and negative sFlt-1/PlGF, group C+/-; and a double positive result, group D+/+. The primary outcome was the proportion of false negatives of the combined tests in comparison with PCr alone in the first week after baseline. Secondary, a cost analysis comparing the costs and savings of adding the sFlt-1/PlGF ratio was performed for different follow-up scenarios. RESULTS: A total of 199 women were included. Pre-eclampsia in the first week was observed in 2 women (2%) in group A-/-, 12 (26%) in group B-/+, 4 (27%) in group C+/-, and 12 (92%) in group D+/+. The proportion of false negatives of 8.2% [95% CI 4.9-13.3] with the PCr alone was significantly reduced to 1.6% [0.4-5.7] by adding a negative sFlt-1/PlGF ratio. Furthermore, the addition of the sFlt-1/PlGF ratio to the spot urine PCr, with telemonitoring of women at risk, could result in a reduction of 41% admissions and 36% outpatient visits, leading to a cost reduction of €46,- per patient. CONCLUSIONS: Implementation of the sFlt-1/PlGF ratio in addition to the spot urine PCr, may lead to improved selection of women at low risk and a reduction of hospital care for women with suspected pre-eclampsia. TRIAL REGISTRATION: Netherlands Trial Register (NL8308).

Rastreamento clínico e nutricional de gestantes de alto risco na estratégia de saúde da família de Santa Quitéria - CE / Clinical and nutritional screening of high-risk pregnant women in the family health strategy of Santa Quitéria - CE / Cribado clínico y nutricional de las embarazadas de alto riesgo en la estrategia de salud familiar de Santa Quitéria - CE

Considera-se gestação de alto risco quando a mulher apresenta comorbidade materna e/ou condição sociobiológica que levam as chances de ocorrer alguma intercorrência na evolução natural da gravidez, como hipertensão arterial, diabetes, anemia, alcoolismo e obesidade. É de grande importância o acompanhamento pré-natal com uma equipe de assistência capaz de identificar os problemas antes mesmo que possam ser agravados. O objetivo deste estudo foi rastrear o perfil clínico e nutricional de mulheres com gestação de alto risco na Estratégia de Saúde da Família de Santa Quitéria- CE. Trata-se de um estudo descritivo, com abordagem quantitativa realizado com 33 gestantes. Para a coleta de dados foi utilizado o cartão da gestante e prontuário, o estado nutricional foi avaliado através do peso pré- gestacional contido no cartão e peso atual através da balança. Para análise estatística, foram usados frequências, percentuais, médias e desvio padrão, verificadas por meio dos testes de Kolmogorov-Smirnov e Levene. Para a comparação de médias entre duas categorias, utilizou-se o teste t de Student para amostras independentes. Os resultados mostraram que a maioria tinha o ensino médio como nível de escolaridade, renda igual ou menor que um salário mínimo, multíparas com um ou mais abortos. Em relação às características do estado clínico patológico, as condições mais prevalentes nas gestantes do presente estudo foram hipertensão arterial sistêmica, pré-eclâmpsia, seguidos de DMG e eritoblastose. Excesso de peso antes e durante a gravidez com ganho ponderal de peso adequado. O que demonstra a necessidade de estratégias para a saúde da mulher. É apropriado acionar sinal de alerta no acompanhamento da saúde da mulher também antes da gestação e não somente no pré-natal para que transcorra bem durante e após o parto. PALAVRAS-CHAVE: Estado nutricional; Gestação de alto risco; Assistência Pré-Natal.

High-risk pregnancy is considered when the woman presents maternal comorbidity and/or sociobiological condition that increase the chances of some complication occurring in the natural evolution of pregnancy, such as arterial hypertension, diabetes, anemia, alcoholism, and obesity; It is of great importance the prenatal follow-up with an assistance team capable of identifying the problems even before they can be aggravated; The objective of this study was to track the clinical and nutritional profile of women with high-risk pregnancy in the Family Health Strategy of Santa Quitéria-CE; This is a descriptive study with a quantitative approach carried out with 33 pregnant women; For data collection the pregnant woman's card and medical records were used, the nutritional status was evaluated through the pre-gestational weight contained in the card and current weight through the scale; For statistical analysis, frequencies, percentages, means and standard deviation were used, verified by means of the Kolmogorov-Smirnov and Levene tests;For comparison of means between two categories, Student's t test for independent samples was used; The results showed that most had high school education, income equal to or less than one minimum wage, multiparous women with one or more abortions; Regarding the characteristics of the pathological medical condition, the most prevalent conditions in the pregnant women of the present study were hypertension, pre- eclampsia, followed by GDM and erythoblastosis; Overweight before and during pregnancy with adequate weight gain; This demonstrates the need for women's health strategies; It is appropriate to trigger warning signals in the monitoring of women's health also before pregnancy and not only in the prenatal period so that it goes well during and after delivery;

Se considera embarazo de alto riesgo cuando la mujer presenta comorbilidad materna y/o condición socio-biológica que conlleva las posibilidades de aparición de alguna complicación en la evolución natural del embarazo, como son la hipertensión, la diabetes, la anemia, el alcoholismo y la obesidad. Es de gran importancia el seguimiento prenatal con un equipo de asistencia capaz de identificar los problemas incluso antes de que puedan agravarse. El objetivo de este estudio fue rastrear el perfil clínico y nutricional de las mujeres con embarazo de alto riesgo en la Estrategia de Salud Familiar de Santa Quitéria-CE. Se trata de un estudio descriptivo con un enfoque cuantitativo realizado con 33 mujeres embarazadas. Para la recopilación de datos se utilizó el cartón de la gestante y el prontuario, el estado nutricional se evaluó a través del peso pregestacional contenido en el cartón y el peso actual a través de la balanza. Para el análisis estadístico se utilizaron frecuencias, porcentajes, medias y desviación estándar, verificados mediante las pruebas de Kolmogorov-Smirnov y Levene. Para la comparación de medias entre dos categorías, se utilizó la prueba t de Student para muestras independientes. Los resultados mostraron que la mayoría tenía estudios secundarios, ingresos iguales o inferiores a un salario mínimo, mujeres multíparas con uno o más abortos. En cuanto a las características del estado clínico patológico, las condiciones más prevalentes en las embarazadas del presente estudio fueron la hipertensión arterial sistémica, la preeclampsia, seguidas de la DMG y la eritoblastosis. Exceso de peso antes y durante el embarazo con un aumento de peso adecuado. Lo que demuestra la necesidad de estrategias de salud para las mujeres. Es conveniente activar la señal de alarma en el seguimiento de la salud de las mujeres también antes del embarazo y no sólo en la atención prenatal para que funcione bien durante y después del parto.

Assessment of adherence to aspirin for preeclampsia prophylaxis and reasons for nonadherence.

BACKGROUND: Preeclampsia is a hypertensive disease unique to pregnancy and has a significant impact on maternal and neonatal morbidity and mortality. Daily aspirin has been demonstrated to reduce the risk of preeclampsia. The American College of Obstetricians and Gynecologists recommends daily low-dose aspirin, ideally before 16 weeks' gestation, in at-risk patients for preeclampsia risk reduction. This study examined whether patients at-risk for preeclampsia by the American College of Obstetricians and Gynecologists criteria recalled aspirin recommendation and factors associated with treatment adherence. OBJECTIVE: This study examined whether patients at-risk for preeclampsia by the American College of Obstetricians and Gynecologists criteria recalled aspirin recommendation and factors associated with treatment adherence. STUDY DESIGN: This study used an anonymous written survey. Pregnant patients were asked to record self-reported risk factors and to recall recommendation to take aspirin for preeclampsia prophylaxis. Participants were then determined to be high-, moderate-, or low-risk on the basis of the American College of Obstetricians and Gynecologists guidelines. Self-reported adherence to recommendations and factors contributing to the patients' decisions to take or decline aspirin were assessed. Secondary outcomes included demographic characteristics of adherent patients and patients who did not recall aspirin recommendation. RESULTS: A total of 544 surveys were distributed and 500 were returned (91.9% response rate). Of the 104 high-risk pregnancies identified, aspirin was recommended in 60 (57.7%; 95% confidence interval, 0.48-0.67). Of the 269 patients with 2 or more moderate-risk factors, aspirin was recommended for 13 (4.8%; 95% confidence interval, 0.03-0.08). Among the participants who recalled aspirin recommendation, adherence was similar between high-risk (81.7%) and moderate-risk (76.9%) groups (P=.69). Patients with chronic hypertension, a history of preeclampsia or gestational hypertension in a previous pregnancy, and pregestational diabetes mellitus were most likely to report receiving aspirin recommendation (78.8%, 76.5%, 63.8%, and 53.3%, respectively). No high-risk factor was associated with a decreased likelihood of adherence. Nonadherent patients rarely discussed their decision with their medical provider (5.9%). In the 42.3% of high-risk participants who did not recall aspirin recommendation, autoimmune disease, multiple gestation, and kidney disease were the most prevalent risk factors (42.9%, 35.7%, and 25.0%, respectively). CONCLUSION: In the population studied, many at-risk patients, as defined by the American College of Obstetricians and Gynecologists criteria, did not recall recommendations to take aspirin for preeclampsia prophylaxis. This raises concerns for absent or ineffective counseling. Of the patients who recalled aspirin recommendation, most reported adherence, and a history of hypertensive disorders or preeclampsia, autoimmune disease, and pregestational diabetes mellitus were most often associated with adherence. There was no single factor most strongly associated with intentional nonadherence.