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

Coronavirus disease 2019; First trimester; PreeclampsiaCoronavirus 2019; Primer trimestre; PreeclàmpsiaCoronavirus 2019; Primer trimestre; PreeclampsiaIntroduction: 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. Material and methods: 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). Results: 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). Conclusions: 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

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

Aspirin; Placental growth factor; Pre-eclampsiaAspirina; Factor de crecimiento placentario; PreeclampsiaAspirina; Factor de creixement placentari; PreeclampsiaIntroduction 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. Material and methods 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. Results 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. Conclusions 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

The Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) Trial to Avoid Adverse Perinatal Outcomes: Protocol for a Multicenter, Open-Label, Randomized Controlled Trial

Angiogenic factors; Fetal growth restriction; Small for gestational ageFactores angiogénicos; Restricción del crecimiento fetal; Pequeño para la edad gestacionalFactors angiogènics; Restricció del creixement fetal; Petit per a l'edat gestacionalBackground: Fetal smallness affects 10% of pregnancies. Small fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37 to 38 weeks. On the other hand, classification using angiogenic factors seems to have a lower false-positive rate. Here, we present a protocol for the Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) trial, which compares the use of angiogenic factors and Doppler to manage small fetuses at term. Objective: The primary objective is to demonstrate that classification based on angiogenic factors is not inferior to estimated fetal weight and Doppler at detecting fetuses at risk of adverse perinatal outcomes. Methods: This is a multicenter, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1030 singleton pregnancies with an estimated fetal weight ≤10th percentile at 36+0 to 37+6 weeks+days will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio ≥38 will be classified as having fetal growth restriction; otherwise, they will be classified as being small for gestational age. In both arms, the fetal growth restriction group will be delivered at ≥37 weeks and the small for gestational age group at ≥40 weeks. We will assess differences between the groups by calculating the relative risk, the absolute difference between incidences, and their 95% CIs. Results: Recruitment for this study started on September 28, 2020. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences in early 2023. Conclusions: The angiogenic factor-based protocol may reduce the number of pregnancies classified as having fetal growth restriction without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities

Risk Factors for Preeclampsia: Results from a Cohort of Over 5000 Pregnancies in Spain.

Objective: To determine the incidence of preeclampsia (PE) and preterm PE in Spain and to identify the risk factors for developing the disease. Methods: This is a multicenter prospective cohort study performed at six maternity units across Spain. Women with singleton pregnancies attending their first-trimester routine visit at the hospital were offered participation. Maternal and pregnancy characteristics, including mean arterial pressure, as well as ultrasound findings were recorded. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for subsequent development of PE. Results:A total of 5868 pregnancies were recruited for this study, including 174 (3.0%) cases of PE, 47 (0.8%) cases of preterm PE and 127 (2.2%) cases of term PE. Median maternal age was 33.9 years (interquartile range: 30.1 to 36.9) and median gestational age at the routine visit was 12.7 weeks (interquartile range: 12.3 to 13.0). However, 293 (5.0%) of the women were on aspirin treatment during pregnancy, likely reducing the true incidence of the disease. As expected, increasing body mass index (P<0.001), uterine artery pulsatility index (P=0.011) and mean arterial pressure (P<0.001), assisted conception (P=0.013), previous personal (P<0.001) or family history of PE (P=0.024) and chronic hypertension (P=0.001) were identified as independent risk factors for developing subsequent PE during pregnancy. Screening for PE by maternal factors alone leads to a detection rate of 36.8% (64/174) at 10.0% (587/5868) screen positive rate. Conclusion: In Spain, 3.0% of singleton pregnancies are complicated by PE and 0.8% require delivery before term due to its severity. Screening of PE by risk factors alone is only able to detect about 40% of total PE at 10% screen-positive rate.post-print255 K

Diagnostic accuracy of first-trimester combined screening for early-onset and preterm pre-eclampsia at 8-10 compared with 11-13 weeks' gestation

To compare the ability of first-trimester combined screening for pre-eclampsia (PE) to predict early-onset and preterm PE when pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) were assessed before vs after 11 weeks' gestation. This was a secondary analysis of a prospective cohort study of singleton pregnancies undergoing routine first-trimester screening conducted at Vall d'Hebron University Hospital, Barcelona, Spain, between October 2015 and September 2017. Demographic characteristics, obstetric history, maternal history and biophysical markers (mean uterine artery pulsatility index and mean arterial blood pressure (MAP)) were recorded at the first-trimester scan (at 11 + 0 to 13 + 6 weeks' gestation). Maternal serum concentrations of PAPP-A and PlGF were assessed from the routine first-trimester blood test (at 8 + 0 to 13 + 6 weeks). Women were classified into two groups depending on whether serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks or at 11 + 0 to 13 + 6 weeks. Probability scores for early-onset and preterm PE were calculated by using two different algorithms: the multivariate Gaussian-distribution model and The Fetal Medicine Foundation (FMF) competing-risks model. Receiver-operating-characteristics (ROC) curves were produced and detection rates at fixed 5% and 10% false-positive rates were computed to compare the performance of these algorithms when PAPP-A and PlGF were assessed before vs after 11 weeks. Of the 2641 women included, serum biomarkers were assessed before 11 weeks in 1675 (63.4%) and at or after 11 weeks in 966 (36.6%). Of these, 90 (3.4%) women developed PE, including 11 (0.4%) cases of early-onset PE and 30 (1.1%) of preterm PE. Five (45.5%) cases of early-onset and 16 (53.3%) of preterm PE were identified in the group in which serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks and six (54.5%) cases of early-onset and 14 (46.7%) of preterm PE in the group in which serum biomarkers were assessed at 11 + 0 to 13 + 6 weeks. In the prediction of early-onset and preterm PE using the Gaussian algorithm, no differences were observed between the areas under the ROC curves (AUCs) when PAPP-A and PlGF were measured before or after 11 weeks. In the prediction of early-onset and preterm PE using the FMF algorithm, no differences were observed between AUCs for any of the combinations used for risk calculation when the serum biomarkers were obtained before vs after 11 weeks, except for the combination of PAPP-A and MAP, which showed a greater AUC for the prediction of early-onset PE when PAPP-A was measured at or after 11 weeks. The prediction of early-onset and preterm PE is similar when serum biomarkers are measured before or after 11 weeks. This allows the use of a two-step approach for PE risk assessment that permits immediate risk calculation at the time of the first-trimester scan. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology

Gestational age-based reference ranges for cervical length and preterm birth prediction in triplet pregnancies: an observational retrospective study

Cervical length; Preterm delivery; Triplet pregnancyLongitud cervical; Parto prematuro; Embarazo de trillizosLongitud cervical; Part prematur; Embaràs de trillissosObjectives To develop gestational age-based reference ranges for cervical length in triplet pregnancies. The secondary objective was to assess the performance of cervical length measured between 18 and 20 + 6 days for the prediction of preterm delivery before 28 and 32 weeks, respectively. Methods Observational retrospective study of triplet pregnancies in three Spanish tertiary-care hospitals between 2001 and 2019. Cervical length measurements were consecutively obtained between 15 and 34 weeks of gestation. Pregnancies undergoing multifetal reduction or fetal surgery were excluded. Results Two hundred and six triplet pregnancies were included in the final analysis. There was a quadratic decrease in cervical length with gestational age. The median and fifth centiles for cervical length at 20 weeks were 35 and 13 mm. In the prediction of preterm birth < 28 weeks, for a false positive rate of 5%, and 10%, the detection rates were 40.9%, and 40.9%, respectively, and the prediction of preterm birth < 32 weeks, 22.0% and 26.0%, respectively. Conclusions In triplet pregnancies, cervical length decreases with gestational age. The performance of cervical length at 18–20 + 6 in screening for preterm birth before 28 and 32 weeks is poor

SARS-CoV-2 T-cell response in COVID-19 convalescent patients with and without lung sequelae

A specific T-cell response persists in the majority of COVID-19 patients 6 months after hospital discharge. This response is more prominent in those who required critical care during the acute COVID-19 episode but is reduced in patients with lung sequelae

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

Abnormal Maternal Body Mass Index and Customized Fetal Weight Charts : Improving the Identification of Small for Gestational Age Fetuses and Newborns

Background: Obesity and thinness are serious diseases, but cases with abnormal maternal weight have not been excluded from the calculations in the construction of customized fetal growth curves (CCs). Method: To determine if the new CCs, built excluding mothers with an abnormal weight, are better than standard CCs at identifying SGA. A total of 16,122 neonates were identified as SGA, LGA, or AGA, using the two models. Logistic regression and analysis of covariance were used to calculate the OR and CI for adverse outcomes by group. Gestational age was considered as a covariable. Results: The SGA rates by the new CCs and by the standard CCs were 11.8% and 9.7%, respectively. The SGA rate only by the new CCs was 18% and the SGA rate only by the standard CCs was 0.01%. Compared to AGA by both models, SGA by the new CCs had increased rates of cesarean section, (OR 1.53 (95% CI 1.19, 1.96)), prematurity (OR 2.84 (95% CI 2.09, 3.85)), NICU admission (OR 5.41 (95% CI 3.47, 8.43), and adverse outcomes (OR 1.76 (95% CI 1.06, 2.60). The strength of these associations decreased with gestational age. Conclusion: The use of the new CCs allowed for a more accurate identification of SGA at risk of adverse perinatal outcomes as compared to the standard CC