Prospective Validation of First-Trimester Screening for Preterm Preeclampsia in Nulliparous Women (PREDICTION Study).

BACKGROUND: Fetal Medicine Foundation (FMF) studies suggest that preterm preeclampsia can be predicted in the first trimester by combining biophysical, biochemical, and ultrasound markers and prevented using aspirin. We aimed to evaluate the FMF preterm preeclampsia screening test in nulliparous women. METHODS: We conducted a prospective multicenter cohort study of nulliparous women recruited at 11 to 14 weeks. Maternal characteristics, mean arterial blood pressure, PAPP-A (pregnancy-associated plasma protein A), PlGF (placental growth factor) in maternal blood, and uterine artery pulsatility index were collected at recruitment. The risk of preterm preeclampsia was calculated by a third party blinded to pregnancy outcomes. Receiver operating characteristic curves were used to estimate the detection rate (sensitivity) and the false-positive rate (1-specificity) for preterm (<37 weeks) and for early-onset (<34 weeks) preeclampsia according to the FMF screening test and according to the American College of Obstetricians and Gynecologists criteria. RESULTS: We recruited 7554 participants including 7325 (97%) who remained eligible after 20 weeks of which 65 (0.9%) developed preterm preeclampsia, and 22 (0.3%) developed early-onset preeclampsia. Using the FMF algorithm (cutoff of ≥1 in 110 for preterm preeclampsia), the detection rate was 63.1% for preterm preeclampsia and 77.3% for early-onset preeclampsia at a false-positive rate of 15.8%. Using the American College of Obstetricians and Gynecologists criteria, the equivalent detection rates would have been 61.5% and 59.1%, respectively, for a false-positive rate of 34.3%. CONCLUSIONS: The first-trimester FMF preeclampsia screening test predicts two-thirds of preterm preeclampsia and three-quarters of early-onset preeclampsia in nulliparous women, with a false-positive rate of ≈16%. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02189148.

Comparison of National Factor-based Models for Preeclampsia Screening.

OBJECTIVE: This study aimed to compare the predictive values of the American College of Obstetricians and Gynecologists (ACOG), the National Institute for Health and Care Excellence (NICE), and the Society of Obstetricians and Gynecologists of Canada (SOGC) factor-based models for preeclampsia (PE) screening. STUDY DESIGN: We conducted a secondary analysis of maternal and birth data from 32 hospitals. For each delivery, we calculated the risk of PE according to the ACOG, the NICE, and the SOGC models. Our primary outcomes were PE and preterm PE (PE combined with preterm birth) using the ACOG criteria. We calculated the detection rate (DR or sensitivity), the false positive rate (FPR or 1 - specificity), the positive (PPV) and negative (NPV) predictive values of each model for PE and for preterm PE using receiver operator characteristic (ROC) curves. RESULTS: We used 130,939 deliveries including 4,635 (3.5%) cases of PE and 823 (0.6%) cases of preterm PE. The ACOG model had a DR of 43.6% for PE and 50.3% for preterm PE with FPR of 15.6%; the NICE model had a DR of 36.2% for PE and 41.3% for preterm PE with FPR of 12.8%; and the SOGC model had a DR of 49.1% for PE and 51.6% for preterm PE with FPR of 22.2%. The PPV for PE of the ACOG (9.3%) and NICE (9.4%) models were both superior than the SOGC model (7.6%; p < 0.001), with a similar trend for the PPV for preterm PE (1.9 vs. 1.9 vs. 1.4%, respectively; p < 0.01). The area under the ROC curves suggested that the ACOG model is superior to the NICE for the prediction of PE and preterm PE and superior to the SOGC models for the prediction of preterm PE (all with p < 0.001). CONCLUSION: The current ACOG factor-based model for the prediction of PE and preterm PE, without considering race, is superior to the NICE and SOGC models. KEY POINTS: · Clinical factor-based model can predict PE in approximately 44% of the cases for a 16% false positive.. · The ACOG model is superior to the NICE and SOGC models to predict PE.. · Clinical factor-based models are better to predict PE in parous than in nulliparous..

Aspirin at 75 to 81 mg Daily for the Prevention of Preterm Pre-Eclampsia: Systematic Review and Meta-Analysis.

Background: Aspirin at 150 mg daily, initiated in the 1st trimester of pregnancy, prevents preterm pre-eclampsia. We aimed to estimate whether a dose of 75 to 81 mg daily can help to prevent preterm pre-eclampsia as well. Methods: A systematic search was conducted using multiple databases and meta-analyses of randomized controlled trials (RCTs) that compared aspirin initiated in the first trimester of pregnancy to placebo or no treatment, following the PRISMA guidelines and the Cochrane risk of bias tool. Results: We retrieved 11 RCTs involving 13,981 participants. Five RCTs had a low risk of bias, one at unclear risk, and fiver had a high risk of bias. A pooled analysis demonstrated that doses of 75 to 81 mg of aspirin, compared to a placebo or no treatment, was not associated with a significant reduction in preterm pre-eclampsia (8 studies; 12,391 participants; relative risk, 0.66; 95% confidence interval: 0.27 to 1.62; p = 0.36), but there was a significant heterogeneity across the studies (I2 = 61%, p = 0.02). Conclusion: It cannot be concluded that taking 75 to 81 mg of aspirin daily reduces the risk of preterm pre-eclampsia. However, given the significant heterogeneity between the studies, the true effect that such a dose of aspirin would have on pregnancy outcomes could not be properly estimated.

Perinatal morbidity among women with a previous caesarean delivery (PRISMA trial): a cluster-randomised trial.

BACKGROUND: Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery. METHODS: We conducted an open, multicentre, cluster-randomised, controlled trial of a multifaceted 2-year intervention in 40 hospitals in Quebec among women with one previous caesarean delivery, in which hospitals were the units of randomisation and women the units of analysis. Randomisation was stratified according to level of care, using blocked randomisation. Hospitals were randomly assigned (1:1) to the intervention group (implementation of best practices and provision of tools that aimed to support decision making about mode of delivery, including an estimation of the probability of vaginal delivery and an ultrasound estimation of the risk of uterine rupture), or the control group (no intervention). The primary outcome was a composite risk of major perinatal morbidity. This trial was registered with ISRCTN, ISRCTN15346559. FINDINGS: 21 281 eligible women delivered during the study period, from April 1, 2016 to Dec 13, 2019 (10 514 in the intervention group and 10 767 in the control group). None were lost to follow-up. There was a significant reduction in the rate of major perinatal morbidity from the baseline period to the intervention period in the intervention group as compared with the control group (adjusted odds ratio [OR] for incremental change over time, 0·72 [95% CI 0·52-0·99]; p=0·042; adjusted risk difference -1·2% [95% CI -2·0 to -0·1]). Major maternal morbidity was significantly reduced in the intervention group as compared with the control group (adjusted OR 0·54 [95% CI 0·33-0·89]; p=0·016). Minor perinatal and maternal morbidity, caesarean delivery, and uterine rupture rates did not differ significantly between groups. INTERPRETATION: A multifaceted intervention supporting women in their choice of mode of delivery and promoting best practices resulted in a significant reduction in rates of major perinatal and maternal morbidity, without an increase in the rate of caesarean or uterine rupture. FUNDING: Canadian Institutes of Health Research (CIHR, MOP-142448).

Impact of COVID-19 and Vaccination During Pregnancy on Placenta-Mediated Complications (COVIGRO Study).

OBJECTIVES: COVID-19 has been associated with preterm birth (PTB) and placental-mediated complications, including fetal growth restriction and preeclampsia (PE). This study aimed to estimate the impact of COVID-19 and vaccination on adverse pregnancy outcomes and markers of placental function. METHODS: We performed a study on a prospective cohort of women recruited in the first trimester of pregnancy during the early COVID-19 pandemic period (December 2020 to December 2021). At each trimester of pregnancy, the assessment included a questionnaire on COVID-19 and vaccination status; serological tests for COVID-19 (for asymptomatic infection); measurement of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in maternal blood; measurement of mean uterine artery pulsatility index (UtA-PI); and pregnancy outcomes (PTB, PE, birth weight below the fifth and the tenth percentile). RESULTS: Among 788 patients with complete data, we observed 101 (13%) cases of symptomatic infection and 74 (9%) cases of asymptomatic infection with SARS-CoV-2. Most cases (73%) of infection were among women with previous vaccination or COVID-19 infection before pregnancy. COVID-19 infection was not associated with adverse pregnancy outcomes, abnormal fetal growth, sFlt-1/PlGF ratio, or mean UtA-PI. Vaccination during pregnancy did not influence these outcomes either. We observed no case of severe COVID-19 infection requiring respiratory support. CONCLUSION: Mild symptomatic or asymptomatic COVID-19 during pregnancy did not influence the risk of adverse pregnancy outcomes and the markers of placental function in predominantly vaccinated women. Fetal growth monitoring is unlikely to be mandatory in women with mild symptoms of COVID-19.

Clinical Risk Factors for Placenta Accreta or Placenta Percreta: A Case-Control Study.

OBJECTIVES: Uterine scarring is a risk factor for placenta accreta spectrum (PAS) disorder. We aimed to determine the factors related to PAS in women who had previously undergone a cesarean. METHODS: We performed a case-control study where women who underwent postpartum hysterectomy for placenta accreta/percreta (cases) were matched to all women with a previous cesarean who delivered in the week before each case (controls). Maternal characteristics along with previous cesarean characteristics were compared between cases and controls. Univariate and multivariate logistic regression analyses were performed to determine risk factors related to PAS. RESULTS: We compared 64 cases of PAS that required hysterectomy to 192 controls. The factors related to PAS were a history of uterine surgery (OR 27.4; 95% CI 5.1-146.5, P < 0.001) and the number of previous cesareans (2 cesareans: OR 7.2; 95% CI 3.4-15.4, P < 0.001; more than 2 cesareans: OR 7.9; 95% CI 2.9-21.5, P < 0.001). In women with a single previous cesarean without previous uterine surgery, an interdelivery interval of fewer than 18 months (OR 6.3; 95% CI 1.8-22.4, P = 0.004) and smoking (OR 5.8; 95% CI 1.2-27.8, P = 0.03) were related to PAS. The gestational age and the cervical dilatation at previous cesarean were not associated with PAS (all with P > 0.05). The lack of data regarding the closure of the uterus at previous cesareans prevents us from drawing solid conclusions. CONCLUSIONS: Previous uterine surgery, the number of previous cesareans, smoking, and an interdelivery interval of fewer than 18 months after cesarean are significant risk factors for PAS requiring postpartum hysterectomy.

Guideline No. 442: Fetal Growth Restriction: Screening, Diagnosis, and Management in Singleton Pregnancies.

OBJECTIVE: Fetal growth restriction is a common obstetrical complication that affects up to 10% of pregnancies in the general population and is most commonly due to underlying placental diseases. The purpose of this guideline is to provide summary statements and recommendations to support a clinical framework for effective screening, diagnosis, and management of pregnancies that are either at risk of or affected by fetal growth restriction. TARGET POPULATION: All pregnant patients with a singleton pregnancy. BENEFITS, HARMS, AND COSTS: Implementation of the recommendations in this guideline should increase clinician competency to detect fetal growth restriction and provide appropriate interventions. EVIDENCE: Published literature in English was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library through to September 2022 using appropriate controlled vocabulary via MeSH terms (fetal growth retardation and small for gestational age) and key words (fetal growth, restriction, growth retardation, IUGR, FGR, low birth weight, small for gestational age, Doppler, placenta, pathology). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Grey literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Table A1 for definitions and Table A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Obstetricians, family physicians, nurses, midwives, maternal-fetal medicine specialists, radiologists, and other health care providers who care for pregnant patients. TWEETABLE ABSTRACT: Updated guidelines on screening, diagnosis, and management of pregnancies at risk of or affected by FGR. SUMMARY STATEMENTS: RECOMMENDATIONS: Prediction of FGR Prevention of FGR Detection of FGR Investigations in Pregnancies with Suspected Fetal Growth Restriction Management of Early-Onset Fetal Growth Restriction Management of Late-Onset FGR Postpartum management and preconception counselling.

Directive clinique no 442 : Retard de croissance intra-utérin : Dépistage, diagnostic et prise en charge en contexte de grossesse monofœtale.

OBJECTIF: Le retard de croissance intra-utérin est une complication obstétricale fréquente qui touche jusqu'à 10 % des grossesses dans la population générale et qui est le plus souvent due à une pathologie placentaire sous-jacente. L'objectif de la présente directive clinique est de fournir des déclarations sommaires et des recommandations pour appuyer un protocole clinique de dépistage, diagnostic et prise en charge du retard de croissance intra-utérin pour les grossesses à risque ou atteintes. POPULATION CIBLE: Toutes les patientes enceintes menant une grossesse monofœtale. BéNéFICES, RISQUES ET COûTS: La mise en application des recommandations de la présente directive devrait améliorer la compétence des cliniciens quant à la détection du retard de croissance intra-utérin et à la réalisation des interventions indiquées. DONNéES PROBANTES: La littérature publiée a été colligée par des recherches effectuées jusqu'en septembre 2022 dans les bases de données PubMed, Medline, CINAHL et Cochrane Library en utilisant un vocabulaire contrôlé au moyen de termes MeSH pertinents (fetal growth retardation and small for gestational age) et de mots-clés (fetal growth, restriction, growth retardation, IUGR, FGR, low birth weight, small for gestational age, Doppler, placenta, pathology). Seuls les résultats de revues systématiques, d'essais cliniques randomisés ou comparatifs et d'études observationnelles ont été retenus. La littérature grise a été obtenue par des recherches menées dans des sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, des registres d'essais cliniques et des sites Web de sociétés de spécialité médicale nationales et internationales. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Obstétriciens, médecins de famille, infirmières, sages-femmes, spécialistes en médecine fœto-maternelle, radiologistes et autres professionnels de la santé qui prodiguent des soins aux patientes enceintes. RéSUMé POUR TWITTER: Mise à jour de la directive sur le dépistage, le diagnostic et la prise en charge du retard de croissance intra-utérin pour les grossesses à risque ou atteintes. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS: Prédiction du retard de croissance intra-utérin Prévention du retard de croissance intra-utérin Détection du retard de croissance intra-utérin Examens en cas de retard de croissance intra-utérin soupçonné Prise en charge du retard de croissance intra-utérin précoce Prise en charge du retard de croissance intra-utérin tardif Prise en charge du post-partum et consultations préconception.

Comparing aspirin 75 to 81 mg vs 150 to 162 mg for prevention of preterm preeclampsia: systematic review and meta-analysis.

OBJECTIVE: This study aimed to compare 2 aspirin dosage regimens for the prevention of preterm preeclampsia (PE): 75 to 81 mg vs 150 to 162 mg taken daily starting in the first trimester of pregnancy. DATA SOURCES: A systematic search was performed using PubMed, Embase, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials from January 1985 to April 2023. STUDY ELIGIBILITY CRITERIA: The inclusion criteria were randomized controlled trials that compared the effect of 2 aspirin dosage regimens during pregnancy for the prevention of PE initiated in the first trimester of pregnancy. The intervention was an aspirin dosage between 150 and 162 mg daily, and the control was an aspirin dosage between 75 and 81 mg daily. METHODS: Of note, 2 reviewers independently screened all citations, selected studies, and evaluated the risk of bias. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and applied the Cochrane risk of bias tool. The corresponding authors of the included studies were contacted to validate each of the collected results. The primary outcome was the risk of preterm preeclampsia, and the secondary outcomes included term preeclampsia, any preeclampsia regardless of gestational age, and severe preeclampsia. Relative risks with their 95% confidence interval were calculated for each study and pooled for global analysis. RESULTS: Of note, 4 randomized controlled trials were retrieved involving 552 participants. Moreover, 2 randomized controlled trials were at unclear risk of bias, 1 trial at low risk of bias and 1 trial at high risk of bias, which did not have the information for the primary outcome. The pooled analysis demonstrated that an aspirin dosage of 150 to 162 mg was associated with a significant reduction of preterm preeclampsia, compared with an aspirin dosage of 75 to 81 mg (3 studies; 472 participants; relative risk, 0.34; 95% confidence interval, 0.15-0.79; P=.01; I2=0%). There was no significant effect on the risk of term preeclampsia (3 studies; 472 participants; relative risk, 0.57; 95% confidence interval, 0.12-2.64; P=.48; I2=64%) and all preeclampsia (4 studies; 552 participants; relative risk, 0.42; 95% confidence interval, 0.17-1.05; P=.06; I2=58%), but there was a reduction of severe preeclampsia (3 studies; 472 participantst; RR, 0.23; 95% CI, 0.09-0.62; P=.003; I2=0%). CONCLUSION: When initiated in the first trimester of pregnancy, an aspirin dosage of 150 to 162 mg daily was associated with a lower risk of preterm PE than an aspirin dosage of 75 to 81 mg daily. However, the lack of large, high-quality studies limited the clinical scope of the current results taken alone.

First-trimester screening for Down syndrome using quadruple maternal biochemical markers.

OBJECTIVES: Placental growth factor (PlGF) is used for first-trimester preeclampsia screening and could be combined with other biochemical markers for Down syndrome screening. We aim to estimate the predictive value of the combination of pregnancy-associated plasma protein (PAPP-A), free ß-human chorionic gonadotropin (free ß-hCG), placental growth factor (PlGF) and α-fetoprotein (AFP) with and without nuchal translucency. METHODS: Singleton pregnancies recruited at 11-14 weeks and followed until delivery. The four maternal markers were measured using Kryptor (ThermoFisher-BRAHMS) and adjusted for gestational age and maternal characteristics. The risk of Down syndrome was calculated using the Fetal Medicine Foundation algorithm and multivariate linear regression analyses in all cases and in 2,200 controls. Receiver-operator characteristic (ROC) curves were used to calculate the detection and false-positive rates. RESULTS: Twenty-six (0.2%) cases of Down syndrome were diagnosed among 13,386 participants. The combination of the four biomarkers could have detected 88% (95% CI: 72-97%) of the cases at a false-positive rate of 13% (95% CI: 12-15%). The addition of nuchal translucency would have increased the detection rate to 96% (95% CI: 82-99%) at a false-positive rate of 4% (95% CI: 4-5%) using a 1:300 cut-off and to 100% (95% CI: 89-100%) at a false-positive rate of 6% (95% CI: 5-8%) using a 1:500 cut-off. CONCLUSIONS: First-trimester screening using biochemical markers allows the identification of approximately 88% of Down syndrome cases for a false-positive rate of 13%. The addition of nuchal translucency raises the detection rate above 95% with a false-positive rate below 5%.

First-trimester diet quality in association with maternal subcutaneous and visceral adipose tissue thicknesses and glucose homeostasis during pregnancy.

We aimed to characterise the associations between first-trimester diet quality, adiposity, and glucose homeostasis measurements throughout pregnancy in a sample of 104 healthy pregnant women. Three Web-based 24-h recalls were completed, from which the Alternate Healthy Eating Index (AHEI) was calculated. At each trimester (12.5 ± 0.7, 22.8 ± 1.0, and 33.6 ± 1.3 weeks of gestation), fasting glucose and insulin were measured to compute an insulin resistance index (HOMA-IR). Subcutaneous and visceral adipose tissue thicknesses were estimated by ultrasound at the end of the first trimester. Inverse associations were observed between the first-trimester AHEI and first-trimester fasting insulin (r = 0.24; p < 0.05), and HOMA-IR (r = -0.22; p < 0.05), as well as third-trimester fasting insulin (r = -0.20; p < 0.05). A trend was also observed between first-trimester AHEI and first-trimester SAT thickness (r = -0.17; p < 0.1). Pre- and early-pregnancy adiposity measurements were identified as high predictors fasting insulin concentrations throughout pregnancy. Higher early-pregnancy diet quality is associated with more favourable metabolic measurements during pregnancy.

Measurement of Lower Uterine Segment Thickness to Detect Uterine Scar Defect: Comparison of Transabdominal and Transvaginal Ultrasound.

OBJECTIVES: Lower uterine segment (LUS) thickness measurement using transabdominal ultrasound (TA-US), transvaginal ultrasound (TV-US), or the combination of both methods can detect scar defect in women with prior cesarean. We aimed to compare the sensitivity of three approaches. METHODS: Women with prior cesarean underwent LUS thickness measurement at 34-38 weeks' gestation. Among those who underwent repeat cesarean before labor, we compared the accuracy of TA-US, TV-US, and the thinner of the two measurements (the "combined measurement") for uterine scar dehiscence using the area under the curve (AUC) of receiver operating curves with their 95% confidence intervals (CI). We calculated the sensitivity and specificity of the three approaches using a cut-off of 2.3 mm based on prior literature. RESULTS: We included 747 participants. The mean LUS thickness was greater with TA-US (3.8 ± 1.6 mm) compared with TV-US (3.5 ± 1.9 mm) or the combined measurement (3.2 ± 1.5 mm; P < .001). The AUC was 78% (95% CI: 69%-87%), 85% (95% CI: 79%-91%), and 88% (95% CI: 82%-93%), respectively (all with P < .001). The AUC difference between TA-US and the combined measurement was not significant (P = .057). A LUS below 2.3 mm would have predicted 9 (45%) of the 20 cases of uterine scar dehiscence using TA-US, 17 (85%) using TV-US, and 18 (90%) using the combined measurement (P < .01). CONCLUSION: The choice of ultrasound approach influences the measurement of the LUS thickness. The combination of the TA-US and TV-US seems to be superior for the detection of uterine dehiscence.