Angiogenic factors for planning fetal surveillance in fetal growth restriction and small-for-gestational-age fetuses : A prospective observational study

The aim of this study was to assess the added value of the soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio for adjusting the periodicity of ultrasound examinations in early-onset fetal growth restriction (FGR) and small for gestational age (SGA). A prospective, observational study. Tertiary referral hospital. One hundred and thirty-four single pregnancies with ultrasonographic estimated fetal weight (EFW) below the 10th centile between 20 +0 and 31 +6 weeks of gestation with antegrade umbilical artery flow. The time from Doppler and sFlt-1/PlGF assessment to delivery was recorded and classified into four ranges: 85 required an elective delivery before 1 week. sFlt-1/PlGF values in early-onset SGA and FGR are predictive of the time to delivery and could be used for planning fetal surveillance, by reducing the frequency of ultrasound in cases with sFlt-1/PlGF 85. sFlt-1/PlGF values in early-onset SGA/FGR could be used in addition to Doppler for planning fetal surveillance. sFlt-1/PlGF values in early-onset SGA/FGR could be used in addition to Doppler for planning fetal surveillance. Linked article : This article is commented on by Cecilia Villalaín, pp. 1878 in this issue. To view this minicommentary visi

First-trimester screening for pre-eclampsia and small for gestational age : A comparison of the gaussian and Fetal Medicine Foundation algorithms

Pre-eclampsia (PE) and small for gestational age (SGA) can be predicted from the first trimester. The most widely used algorithm worldwide is the Fetal Medicine Foundation (FMF) algorithm. The recently described Gaussian algorithm has reported excellent results although it is unlikely to be externally validated. Therefore, as an alternative approach, we compared the predictive accuracy for PE and SGA of the Gaussian and FMF algorithms. Secondary analysis of a prospective cohort study was conducted at Vall d'Hebron University Hospital (Barcelona) with 2641 singleton pregnancies. The areas under the curve for the predictive performance for early-onset and preterm PE and early-onset and preterm SGA were calculated with the Gaussian and FMF algorithms and subsequently compared. The FMF and Gaussian algorithms showed a similar predictive performance for most outcomes and marker combinations. Nevertheless, significant differences for early-onset PE prediction favored the Gaussian algorithm in the following combinations: mean arterial blood pressure (MAP) with pregnancy-associated plasma protein A, MAP with placental growth factor, and MAP alone. The first-trimester Gaussian and FMF algorithms have similar performances for PE and SGA prediction when applied with all markers within a routine care setting in a Spanish population, adding evidence to the external validity of the FMF algorithm. The first-trimester Gaussian and Fetal Medicine Foundation algorithms have similar predictive performances for pre-eclampsia and small-for-gestational-age fetuses

Confirmation of preeclampsia-like syndrome induced by severe COVID-19 : An Observational Study

Since the outbreak of the COVID-19 pandemic, some studies have reported an increased preeclampsia (PE) incidence in pregnant women with SARS-CoV-2 infection. Several explanations for this association have been proposed, including a preeclampsia-like syndrome induced by severe COVID-19. This syndrome was described in a small case series and has not been confirmed in larger studies and its impact in perinatal outcomes has not been studied. The aim of this study was to confirm the preeclampsia-like syndrome due to COVID-19 and to investigate its implications in pregnancy outcomes and prognosis. This was a prospective, observational study conducted in a tertiary referral hospital. Inclusion criteria were pregnant women admitted to the Intensive Care Unit for severe pneumonia due to COVID-19. They were classified in three groups based on clinical and laboratory findings: PE, PE-like syndrome, and women without PE features. The three cohorts were analyzed and compared at three different times: before, during and after severe pneumonia. The main outcomes were incidence of adverse perinatal outcomes and signs and symptoms of PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes and increased angiogenic factors (soluble fms-like tyrosine kinase-1 to placental growth factor ratio [sFlt-1/PlGF]). A total of 106 women were admitted to Intensive Care Unit due to severe pneumonia and 68 were included in the study. Of those, 53 (50.0%) did not meet the diagnostic criteria for PE and remained pregnant after pneumonia (non-PE), seven (6.6%) met the diagnostic criteria for PE, had abnormal (>38) sFlt-1/PlGF (PE) and delivered during severe pneumonia, and eight (7.5%) met the diagnostic criteria for PE, had normal (≤38) sFlt-1/PlGF (PE-like) and did not deliver during pneumonia. Despite not having delivered, most PE-related features improved after severe pneumonia in women with PE-like syndrome. Women with PE had significantly poorer outcomes than women with PE-like syndrome or without PE. More than 50% of women with severe COVID-19 and diagnostic criteria for PE may not be PE but a PE-like syndrome, which may affect up to 7.5% of women with severe COVID-19. PE-like syndrome might have similar perinatal outcomes to those of normotensive women with severe pneumonia due to COVID-19. For these reasons, PE-like syndrome should be excluded by using sFlt-1/PlGF in future research and before making clinical decisions

First-trimester screening for pre-eclampsia and small for gestational age: A comparison of the gaussian and Fetal Medicine Foundation algorithms

Preeclampsia d'inici precoç; Primer trimestreEarly-onset pre-eclampsia; First trimesterPreeclampsia de inicio precoz; Primer trimestreObjective Pre-eclampsia (PE) and small for gestational age (SGA) can be predicted from the first trimester. The most widely used algorithm worldwide is the Fetal Medicine Foundation (FMF) algorithm. The recently described Gaussian algorithm has reported excellent results although it is unlikely to be externally validated. Therefore, as an alternative approach, we compared the predictive accuracy for PE and SGA of the Gaussian and FMF algorithms. Methods Secondary analysis of a prospective cohort study was conducted at Vall d'Hebron University Hospital (Barcelona) with 2641 singleton pregnancies. The areas under the curve for the predictive performance for early-onset and preterm PE and early-onset and preterm SGA were calculated with the Gaussian and FMF algorithms and subsequently compared. Results The FMF and Gaussian algorithms showed a similar predictive performance for most outcomes and marker combinations. Nevertheless, significant differences for early-onset PE prediction favored the Gaussian algorithm in the following combinations: mean arterial blood pressure (MAP) with pregnancy-associated plasma protein A, MAP with placental growth factor, and MAP alone. Conclusions The first-trimester Gaussian and FMF algorithms have similar performances for PE and SGA prediction when applied with all markers within a routine care setting in a Spanish population, adding evidence to the external validity of the FMF algorithm

Confirmation of preeclampsia-like syndrome induced by severe COVID-19: an observational study

COVID-19; Preeclampsia; PregnancyCOVID-19; Preeclampsia; EmbarazoCOVID-19; Preeclampsia; EmbaràsBACKGROUND Since the outbreak of the COVID-19 pandemic, some studies have reported an increased preeclampsia incidence in pregnant women with SARS-CoV-2 infection. Several explanations for this association have been proposed, including a preeclampsia-like syndrome induced by severe COVID-19. This syndrome was described in a small case series and has not been confirmed in larger studies, and its effect on perinatal outcomes has not been studied. OBJECTIVE This study aimed to confirm the preeclampsia-like syndrome because of COVID-19 and to investigate its implications on pregnancy outcomes and prognosis. STUDY DESIGN This was a prospective, observational study conducted in a tertiary referral hospital. The inclusion criteria were pregnant women admitted to the intensive care unit for severe pneumonia because of COVID-19. They were classified into 3 groups based on clinical and laboratory findings: preeclampsia, preeclampsia-like syndrome, and women without preeclampsia features. The 3 cohorts were analyzed and compared at 3 different times: before, during, and after severe pneumonia. The main outcomes were incidence of adverse perinatal outcomes and signs and symptoms of PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, and increased angiogenic factors (soluble fms-like tyrosine kinase 1–to–placental growth factor ratio). RESULTS A total of 106 women were admitted to the intensive care unit because of severe pneumonia, and 68 women were included in the study. Of those, 53 (50.0%) did not meet the diagnostic criteria for preeclampsia and remained pregnant after pneumonia (non-preeclampsia); 7 (6.6%) met the diagnostic criteria for preeclampsia, had abnormal (>38) soluble fms-like tyrosine kinase 1–to–placental growth factor ratio (preeclampsia), and delivered during severe pneumonia, and 8 (7.5%) met the diagnostic criteria for preeclampsia, had normal (≤38) soluble fms-like tyrosine kinase 1–to–placental growth factor ratio (preeclampsia like), and did not deliver during pneumonia. Despite not having delivered, most preeclampsia-related features improved after severe pneumonia in women with preeclampsia-like syndrome. Women with preeclampsia had significantly poorer outcomes than women with preeclampsia-like syndrome or without preeclampsia. CONCLUSION More than 50% of women with severe COVID-19 and diagnostic criteria for preeclampsia may not be preeclampsia but a preeclampsia-like syndrome, which may affect up to 7.5% of women with severe COVID-19. Preeclampsia-like syndrome might have similar perinatal outcomes to those of normotensive women with severe pneumonia because of COVID-19. For these reasons, preeclampsia-like syndrome should be excluded by using soluble fms-like tyrosine kinase 1–to–placental growth factor ratio in future research and before making clinical decisions

Clinical effectiveness of routine first-trimester combined screening for pre-eclampsia in Spain with the addition of placental growth factor

Pre-eclampsia affects 2%-8% of pregnancies and is one of the leading causes of maternal and perinatal morbidity and mortality. First-trimester screening using an algorithm that combines maternal characteristics, mean arterial blood pressure, uterine artery pulsatility index and biomarkers (pregnancy-associated plasma protein-A and placental growth factor) is the method that achieves a greater diagnostic accuracy. It has been shown that daily salicylic acid administration before 16 weeks in women at a high risk for pre-eclampsia can reduce the incidence of preterm pre-eclampsia. However, no previous studies have evaluated the impact of routine first-trimester combined screening for pre-eclampsia with placental growth factor after being implemented in the clinical practice. This was a multicenter cohort study conducted in eight different maternities across Spain. Participants in the reference group were prospectively recruited between October 2015 and September 2017. Participants in the study group were retrospectively recruited between March 2019 and May 2021. Pre-eclampsia risk was calculated between 11 +0 and 13 +6 weeks using the Gaussian algorithm combining maternal characteristics, mean arterial pressure, uterine arteries pulsatility index, pregnancy-associated plasma protein-A and placental growth factor. Patients with a risk greater than 1/170 were prescribed daily salicylic acid 150 mg until 36 weeks. Patients in the reference group did not receive salicylic acid during gestation. A significant reduction was observed in preterm pre-eclampsia (OR 0.47; 95% CI: 0.30-0.73), early-onset (<34 weeks) pre-eclampsia (OR 0.35; 95% CI: 0.16-0.77), preterm small for gestational age newborn (OR 0.57; 95% CI: 0.40-0.82), spontaneous preterm birth (OR 0.72; 95% CI: 0.57-0.90), and admission to intensive care unit (OR 0.55; 95% CI: 0.37-0.81). A greater treatment adherence resulted in a significant reduction in adverse outcomes. Routine first-trimester screening for pre-eclampsia with placental growth factor leads to a reduction in preterm pre-eclampsia and other pregnancy complications. Aspirin treatment compliance has a great impact on the effectiveness of this screening program. Routine first-trimester combined screening for pre-eclampsia in Spain with the addition of placental growth factor resulted in a significant reduction of pre-eclampsia and other pregnancy complications

sFlt-1 to PlGF ratio cut-offs to predict adverse pregnancy outcomes in early-onset FGR and SGA: a prospective observational study

This is a prospective, observational study, conducted in a tertiary referral hospital. We enrolled 175 singleton pregnancies with estimated foetal weight below the 10th centile between 20 + 0 and 31 + 6 weeks. Placental growth factor (PlGF), soluble fms‐like tyrosine kinase‐1 (sFlt-1) and fetoplacental circulation were assessed at the time of diagnosis. Receiver operating characteristic curves were used to assess the performance of sFlt-1/PlGF for predicting adverse perinatal outcomes (APO). The optimal cut-offs to predict each adverse outcome were calculated and the resulting areas under the curve (AUC) were compared to those calculated from the cut-off points of 38, 85 and 110. The need for delivery at <30 and <34 weeks and APO were the main outcome measures. The optimal cut-off points to predict APO, delivery <30 and <34 weeks were 24.9, 116.7 and 97.5, respectively. None of them proved to be superior to 38, 85 or 110 for predicting any adverse pregnancy outcome. Impact Statement What is already known on this subject? Soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) are biomarkers of placental dysfunction. High sFlt‐1/PlGF values predict adverse perinatal outcomes in preeclampsia (PE). What do the results of this study add? No specific thresholds have been described to identify early-onset foetal growth restriction (FGR) and small for gestational age (SGA) foetuses at higher risk of adverse outcomes. This study describes these specific cut-offs and compares their predictive capacity to those described for PE. What are the implications of these findings for clinical practice and/or further research? The sFlt-1/PlGF cut-off points of 38, 85 and 110 might be useful for ruling out the occurrence of APO and the need for elective delivery at <30 and at <34 weeks from the moment of diagnosis in early-onset FGR and SGA. These cut-offs could aid Doppler studies in the distinction between FGR and SGA

Shared risk factors for -19 and preeclampsia in the first trimester : An observational study

The association between preeclampsia and coronavirus disease 2019 (COVID-19) is under study. Previous publications have hypothesized the existence of shared risk factors for both conditions or a deficient trophoblastic invasion as possible explanations for this association. The primary aim of this study was to examine baseline risk factors measured in the first-trimester combined screening for preeclampsia in pregnant women with COVID-19 compared with the general population. A secondary aim of this study was to compare risk factors among patients with mild and severe COVID-19. This was an observational retrospective study conducted at Vall d'Hebron Hospital Campus (Catalonia, Spain). Study patients were 231 pregnant women undergoing the first-trimester screening for preeclampsia and positive for severe acute respiratory syndrome coronavirus 2 between February 2020 and September 2021. The reference cohort were 13 033 women of the general population from six centers across Catalonia from May 2019 to June 2021. Based on the need for hospitalization, patients were classified in two groups: mild and severe COVID-19. First-trimester screening for preeclampsia included maternal history, mean arterial blood pressure, mean uterine artery pulsatility index (UtAPI), placental growth factor (PlGF), and pregnancy-associated plasma protein-A (PAPP-A). The proportion of cases at high risk for preeclampsia was significantly higher among the COVID-19 group compared with the general population (19.0% and 13.2%, respectively; p = 0.012). When analyzing risk factors for preeclampsia individually, women with COVID-19 had higher median body mass index (25.2 vs 24.5, p = 0.041), higher UtAPI multiple of the median (MoM) (1.08 vs 1.00, p < 0.001), higher incidence of chronic hypertension (2.8% vs 0.9%, p = 0.015), and there were fewer smokers (5.7% vs 11.6%, p = 0.007). The MoMs of PlGF and PAPP-A did not differ significantly between both groups (0.96 vs 0.97, p = 0.760 and 1.00 vs 1.01, p = 0.432; respectively). In patients with COVID-19, there was a higher proportion of women at high risk for preeclampsia at the first-trimester screening than in the general population, mainly because of maternal risk factors, rather than placental signs of a deficient trophoblastic invasion