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).

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..

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%.

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.

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.

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.

Midtrimester Cervical Length in Low-Risk Nulliparous Women for the Prediction of Spontaneous Preterm Birth: Should We Consider a New Definition of Short Cervix?

OBJECTIVE: The study aimed to estimate the predictive value of midtrimester cervical length (CL) and the optimal cut-off of CL that should be applied with asymptomatic nulliparous women for the prediction of spontaneous preterm birth (sPTB). STUDY DESIGN: This is a prospective cohort study of asymptomatic nulliparous women with a singleton gestation. Participants underwent CL measurement by transvaginal ultrasound between 20 and 24 weeks of gestation. The participants and their health care providers remained blinded to the results of CL measurement. The primary outcomes were sPTB before 35 weeks and sPTB before 37 weeks. Receiver operating characteristics (ROC) curve analyses were performed. Analyses were repeated by using multiples of median (MoM) of CL adjusted for gestational age. RESULTS: Of 796 participants, the mean midtrimester CL was 40 ± 6 mm with a 1st, 5th, and 10th percentile of 25, 29, and 32 mm, respectively. ROC curve analyses suggest that a cut-off of 30 mm was the optimal CL to predict sPTB before 35 weeks (area under the ROC curve [AUC]: 0.70, 95% confidence interval [CI]: 0.56-0.85) and before 37 weeks (AUC: 0.70, 95% CI: 0.59-0.80). Midtrimester CL <30 mm could detect 35% of all sPTB before 35 weeks at a false-positive rate of 5% (relative risk: 9.1, 95% CI: 3.5-23.5, p < 0.001). We observed similar results using a cut-off of CL <0.75 MoM adjusted for gestational age. CONCLUSION: A midtrimester CL cut-off of 30 mm (instead of 25 mm), or CL less than 0.75 MoM, should be used to identify nulliparous women at high risk of sPTB. KEY POINTS: · The optimal CL cut-off for the prediction of sPTB is 30 mm in nulliparous women.. · In nulliparous women, a midtrimester CL < 30 mm is highly associated with sPTB before 35 and 37 weeks.. · A midtrimester of CL <30 mm (5th percentile) should define a short cervix in asymptomatic nulliparous women..

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.

Impact of Third-Trimester Measurement of Low Uterine Segment Thickness and Estimated Fetal Weight on Perinatal Morbidity in Women With Prior Cesarean Delivery.

OBJECTIVES: This study aimed to estimate the impact of third-trimester ultrasound with measurement of the lower uterine segment thickness (LUST) and estimation of fetal weight (EFW) on maternal and perinatal morbidity among women with a prior cesarean delivery. METHODS: We performed a secondary analysis of the QUARISMA trial, including women who delivered at term after one prior cesarean delivery in tertiary care centres. Major and minor maternal and perinatal morbidities were compared between centres that had introduced LUST and EFW measurements into routine practice and those that had not, using generalised estimating equations and adjusted odds ratios (aOR). In a secondary analysis, we compared women who underwent a trial of labour with and without LUST and EFW measurements. RESULTS: We observed a significant reduction in major perinatal morbidity (aOR 0.52; 95% CI 0.28-0.96, P = 0.04), minor perinatal morbidity (aOR 0.49; 95% CI 0.25-0.96, P = 0.04), and minor maternal morbidity (aOR 0.56; 95% CI 0.34- 0.94, P = 0.03) but no significant difference in major maternal morbidity (aOR 0.40; 95% CI 0.04-3.69, P = 0.42) in the 2 centres that had introduced third-trimester ultrasound with EFW and LUST measurements (1458 women), compared with the 4 centres (1247 women) that had not. Among women who underwent a trial of labour, we observed a reduction in major perinatal morbidity (aOR 0.25; 95% CI 0.11-0.54, P < 0.001) and a lower rate of uterine rupture (0% vs. 0.3%, P = 0.045) with LUST and EFW measurements. CONCLUSION: Third-trimester ultrasound with EFW and LUST measurement is associated with a significant reduction in major perinatal morbidity in women with a prior cesarean delivery.

Aspirin Responsiveness at a Dose of 80 mg and Its Impact on Birth Weight when Used in Twin Pregnancies: The GAP Pilot Randomized Trial.

OBJECTIVE: Daily aspirin, started in the first trimester of pregnancy, is commonly used for the prevention of preeclampsia and fetal growth restriction in multiple gestation. However, the optimal dose remains controversial and the evidence for the use of aspirin in multiple pregnancies is scarce. We aimed to estimate the impact of 80 mg of aspirin in twin pregnancies. STUDY DESIGN: We performed a pilot double-blind randomized trial of women with twin pregnancies recruited between 8 and 14 weeks of gestation. Fifty participants (25 in each group) were randomized to 80 mg of aspirin daily at bedtime or a placebo from randomization until 36 weeks of gestation. Primary and secondary outcomes included the birth weight of live infants, preeclampsia, and aspirin responsiveness evaluated by a platelet aggregation test (platelet function assay [PFA]-100). RESULTS: All participants were followed until birth, including 48 and 47 live newborns in the aspirin and the placebo groups, respectively. The mean birth weight difference between the aspirin (2,385 ± 529 g) and placebo (2,224 ± 706 g) groups was of 179 g (95% confidence interval [CI]: -172-531 g, p = 0.32). We observed two (8%) cases of preeclampsia in the aspirin group and no case with placebo (p = 0.49). Most importantly,16 of 24 participants who received aspirin (67%; 95% CI: 45-84%) had a normal PFA-100 test at 22 to 23 weeks, including the two cases of preeclampsia, suggesting that the majority of the participants were nonresponsive to 80 mg of aspirin. CONCLUSION: Our results suggest that the majority of women with twin pregnancies showed a lack of response to a daily dose of 80 mg of aspirin according to the PFA-100 test, compared with the expected 29% of nonresponsiveness in singleton pregnancies. A daily dose of 80 mg of aspirin is likely to be insufficient for the prevention of preeclampsia and other placenta-mediated complications in twin pregnancies. KEY POINTS: · Most women with twin pregnancies are nonresponsive to a daily dose of 80-mg aspirin.. · An 80 mg aspirin dose is insufficient to prevent placenta-mediated complications in twin pregnancies.. · Randomized trials using 100 to 160 mg of aspirin in twin pregnancies are needed..

Pregnancy outcomes in nulliparous women with positive first-trimester preterm preeclampsia screening test: the Great Obstetrical Syndromes cohort study.

BACKGROUND: The Fetal Medicine Foundation proposed a competing risks model for early identification of women at a high risk of preterm preeclampsia, typically associated with deep placentation disorders. The Great Obstetrical Syndromes include a spectrum of pregnancy complications (preeclampsia, intrauterine growth restriction, preterm birth, late spontaneous abortion, and abruptio placentae) that are also associated with deep placentation disorders. OBJECTIVE: This study aimed to estimate the rate of placenta-mediated pregnancy complications in nulliparous women with a positive first-trimester Fetal Medicine Foundation preterm preeclampsia screening test. STUDY DESIGN: We conducted a prospective cohort study of nulliparous women recruited at 11 to 14 weeks of gestation. Maternal characteristics, mean arterial blood pressure, levels of maternal serum biomarkers (pregnancy-associated plasma protein-A, placental growth factor, and soluble fms-like tyrosine kinase-1), and mean uterine artery pulsatility index were obtained to calculate the risk of preterm preeclampsia according to the Fetal Medicine Foundation algorithm. The predicted risks were dichotomized as a positive or negative test according to 2 risk cutoffs (1 in 70 and 1 in 100). The detection rate, false-positive rate, and positive and negative predictive values were calculated for placenta-mediated complications, including preeclampsia, small for gestational age (birthweight <10th percentile), fetal death, preterm birth, and a composite outcome, including any of the foregoing. The same analyses were computed for a composite of severe outcomes, including preterm preeclampsia, severe small for gestational age (less than third percentile), and fetal death. RESULTS: We included 4575 participants with complete observations, of whom 494 (10.8%) had an estimated risk of preterm preeclampsia of ≥1 in 70 and 728 (15.9%) had a risk of ≥1 in 100. The test based on a risk cutoff of 1 in 70 could have correctly predicted up to 27% of preeclampsia, 55% of preterm preeclampsia, 18% of small for gestational age, 24% of severe small for gestational age, and 37% of fetal deaths at a 10% false-positive rate. The test based on a cutoff of 1 in 100 could have predicted correctly up to 35% of preeclampsia, 69% of preterm preeclampsia, 25% of small for gestational age, 30% of severe small for gestational age, and 53% of fetal deaths at a 15% false-positive rate. The positive predictive value of a screening test for preterm preeclampsia of ≥1 in 70 was 3% for preterm preeclampsia, 32% for the composite outcome, and 9% for the severe composite outcome. CONCLUSION: Nulliparous women with a first-trimester positive preterm preeclampsia Fetal Medicine Foundation screening test are at a higher risk of both preterm preeclampsia and other severe placenta-mediated pregnancy complications. Approximately 1 woman of 10 identified as high risk by the Fetal Medicine Foundation algorithm developed at least 1 severe placenta-mediated pregnancy complication.

First-Trimester Preterm Preeclampsia Screening in Nulliparous Women: The Great Obstetrical Syndrome (GOS) Study.

OBJECTIVES: To estimate the ability of a combination of first-trimester markers to predict preterm preeclampsia in nulliparous women. METHODS: We conducted a prospective cohort study of nulliparous women with singleton gestations, recruited between 110 and 136 weeks gestation. Data on the following were collected: maternal age; ethnicity; chronic diseases; use of fertility treatment; body mass index; mean arterial blood pressure (MAP); serum levels of pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), alpha fetoprotein (AFP), free beta human chorionic gonadotropin (ß-hCG); and mean uterine artery pulsatility index (UtA-PI). We constructed a proportional hazard model for the prediction of preterm preeclampsia selected based on the Akaike information criterion. A receiver operating characteristic curve was created with the predicted risk from the final model. Our primary outcome was preterm preeclampsia and our secondary outcome was a composite of preeclampsia, small for gestational age, intrauterine death, and preterm birth. RESULTS: Among 4659 nulliparous women with singleton gestations, our final model included 4 variables: MAP MoM, log10PlGF MoM, log10AFP MoM and log10UtA-PI MoM. We obtained an area under the curve of 0.84 (95% CI 0.75-0.93) with a detection rate of preterm preeclampsia of 55% (95% CI 37%-73%) and a false-positive rate of 10%. Using a risk cut-off with a false-positive rate of 10%, the positive predictive value for our composite outcome was 33% (95% CI 29%-37%). CONCLUSIONS: The combination of MAP, maternal serum PlGF and AFP, and UtA-PI are useful to identify nulliparous women at high risk of preterm preeclampsia but also at high risk of other great obstetrical syndromes.

Ultrasonographic Transabdominal Measurement of Uterine Cervical Length for the Prediction of a Midtrimester Short Cervix.

OBJECTIVE: This study was aimed to estimate the value of transabdominal (TA) ultrasound measurement of cervical length (CL), as an alternative of transvaginal (TV) ultrasound, for universal screening of short cervix in the midtrimester. STUDY DESIGN: We conducted a prospective cohort study of nulliparous women with singleton pregnancy at 20 to 24 weeks of gestation. All participants underwent TA ultrasound followed by TV ultrasound with acquisitions of images and videos of the uterine cervix. A second sonographer, blinded to the participants' data and pregnancy outcomes, measured the CL using TA and TV images and videos. Pearson's correlation test and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: A total of 805 participants were recruited, including 780 (97%) where TA CL measurement was feasible. We observed a strong correlation of CL between TA and TV (correlation coefficient: 0.57; p < 0.0001) with a mean TA measurement being 4 mm (95% confidence interval [CI]: -6 to 14 mm) below the mean TV measurement (mean of differences: 5 ± 4 mm). We observed that a TA CL <30 mm was highly predictive of a short cervix defined as a TV CL ≤25 mm (area under the ROC curve: 0.97; 95% CI: 0.95-0.99; p < 0.0001) with a sensitivity of 100% and a false-positive rate of 22%. CONCLUSION: Universal short cervix screening in nulliparous women could be performed using TA ultrasound, which could allow the avoidance of TV ultrasound in more than three quarter of women. In low-risk population, TV ultrasound could be reserved to women with TA CL <30 mm. KEY POINTS: · Cervical length (CL) measurement with transabdominal (TA) ultrasound is feasible in most cases and is strongly correlated with CL measured with transvaginal (TV) ultrasound.. · Using a cut-off of 30 mm for TA ultrasound as a first-step screening of short cervix in nulliparous women, three-quarter of TV ultrasound could have been avoided.. · Use of TA CL screening could alleviate some of the logistical challenges of universal TV CL screening..

Guideline No. 402: Diagnosis and Management of Placenta Previa.

OBJECTIVES: To summarize the current evidence and to make recommendations for diagnosis and classification of placenta previa and for managing the care of women with this diagnosis. OPTIONS: To manage in hospital or as an outpatient and to perform a cesarean delivery preterm or at term or to allow a trial of labour when a diagnosis of placenta previa or a low-lying placenta is suspected or confirmed. OUTCOMES: Prolonged hospitalization, preterm birth, rate of cesarean delivery, maternal morbidity and mortality, and postnatal morbidity and mortality. INTENDED USERS: Family physicians, obstetricians, midwives, and other maternal care providers. TARGET POPULATION: Pregnant women with placenta previa or low-lying placenta. EVIDENCE: Medline, PubMed, Embase, and the Cochrane Library were searched from inception to October 2018. Medical Subject Heading (MeSH) terms and key words related to pregnancy, placenta previa, low-lying placenta, antepartum hemorrhage, short cervical length, preterm labour, and cesarean. This document represents an abstraction of the evidence rather than a methodological review. VALIDATION METHODS: This guideline has been reviewed by the Maternal-Fetal Medicine and Diagnostic Imaging committees of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and approved by the SOGC Board of Directors. BENEFITS, HARMS, AND/OR COSTS: Women with placenta previa or low-lying placenta are at increased risk of maternal, fetal and postnatal adverse outcomes that include a potentially incorrect diagnosis and possibly unnecessary hospitalization, restriction of activities, early delivery, or cesarean delivery. Optimization of diagnosis and management protocols has potential to improve maternal, fetal and postnatal outcomes. SUMMARY STATEMENTS (GRADE RATINGS IN PARENTHESES): RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

First Trimester Mean Arterial Pressure Measured Manually Versus Using an Automated Device and the Prediction of Preeclampsia: A Case-Cohort Study.

OBJECTIVE: First trimester mean arterial blood pressure (MAP) can be used to predict preeclampsia. This study aimed to compare the performance of first trimester MAP measured with an automated device using a standardized technique versus MAP taken manually in a typical clinical setting. METHODS: A case-cohort study niched into a prospective cohort of pregnant women recruited at 11-14 weeks was performed. MAP was measured with an automated device on both arms until stability was reached. These results were compared with the MAP measured with a manual device at the closest medical visit (between 10 and 15 weeks gestation) and noted in the medical charts. Receiver-operator characteristics curve analyses were used to estimate the predictive values of MAP measured by both techniques. RESULTS: Forty-one women with preeclampsia and 167 control patients were used for the comparisons. MAP measured with an automated device decreased significantly between 11 and 14 weeks gestation (P < 0.001). Moreover, MAP measured with an automated device was a better predictor of preeclampsia (area under the curve 0.70; 95% confidence interval 0.61-0.79) than MAP measured with a manual device in a clinical setting (area under the curve 0.60; 95% confidence interval 0.50-0.70). Taken alone, MAP measured with an automated device was associated with a detection rate of preeclampsia of 34%, for a false-positive rate of 10%. CONCLUSION: First trimester MAP can predict preeclampsia. This study demonstrated that MAP measured with an automated device using a standardized technique is a better predictor than MAP measured with a manual device.

A Pilot Randomized Trial Comparing the Effects of 80 versus 160 mg of Aspirin on Midtrimester Uterine Artery Pulsatility Index in Women with a History of Preeclampsia.

OBJECTIVE: To compare the effects of 80 mg and 160 mg of aspirin, initiated in the first trimester of pregnancy, on mid-trimester uterine artery pulsatility index (UtA-PI) in women with a history of preeclampsia. METHODS: We performed a pilot double-blind randomized controlled trial. Pregnant women with a history of preeclampsia were recruited between 100/7 and 136/7 weeks gestation and randomly assigned to take either 80 or 160 mg of aspirin daily at bedtime from randomization to 356/7 weeks gestation. The primary outcome was mean UtA-PI at 22-24 weeks. Secondary outcomes included the rate of fetal growth restriction and preeclampsia, stratified as term (≥37 weeks), preterm (<37 weeks), and early-onset (<34 weeks) preeclampsia. RESULTS: A total of 107 participants were randomized, including 41 (38%) with a history of preterm preeclampsia and 16 (15%) with a history of early-onset preeclampsia. We observed no significant difference in mean UtA-PI at 22-24 weeks between the 2 groups (0.97; 95% CI 0.88-1.05 vs. 0.97; 95% CI 0.88-1.07, P = 0.9). The rates of fetal growth restriction (8% vs. 2%; P = 0.20); preeclampsia (12% vs. 15%; P = 0.78), preterm preeclampsia (4% vs. 2%; P = 0.56), and early-onset preeclampsia (0% vs. 2%; P = 0.52) were similar in both groups. No serious adverse events associated with the study treatment were reported. CONCLUSION: We observed no significant difference in UtA-PI between the two doses of aspirin, but we observed low rates of fetal growth restriction and preterm and early-onset preeclampsia (all less than 5%). The benefits of aspirin for the prevention of preterm preeclampsia is probably not related to the improvement of deep placentation alone.

Evolution of Down Syndrome Prenatal Screening Clinical Practices in Québec.

OBJECTIVE: Prenatal screening for Down syndrome (DS) has evolved greatly over the last decades with the improvement of first- and second-trimester serum screening and the introduction of cell-free fetal DNA. This study aimed to estimate the impact of such changes on practices. METHODS: This retrospective cohort study included fetuses and newborns diagnosed with DS between 2005-2007 and 2015-2017 in the single obstetrical care centre in Québec City. Data were collected on the prenatal screening method, diagnosis, and delivery. The median was compared between the study periods. RESULTS: Complete clinical data were available for only 78 (66%) of 119 cases of DS. Significant changes were observed in screening methods, including an increase in the use of first-trimester serum, ultrasound, and cell-free fetal DNA. No significant changes were noted in terms of gestational age at diagnosis (median [interquartile range; IQR]: 17.0 [16.0-20.9] weeks in 2005-2007 vs. 17.9 [16.3-22.5] weeks in 2015-2017; P = 0.49) and delivery or termination of pregnancy (median 20.9 [IQR 18.0-23.3] weeks in 2005-2007 vs. 21.3 [18.4-23.4] weeks in 2015-2017; P = 0.46). The methods of diagnosis did not change significantly over the decade, with amniocentesis used 85% and 79% of the time, respectively (P = 0.19). CONCLUSION: The increased use of first-trimester screening and cell-free fetal DNA tests was not associated with earlier diagnosis of DS or earlier delivery or termination of pregnancy. The use of chorionic villus sampling should be encouraged for DS diagnosis when indicated because it could reduce the gestational age at diagnosis and termination if requested.

Placental Growth Factor and Soluble, Fms-Like Tyrosine Kinase-1 in Preeclampsia: A Case-Cohort (PEARL) Study.

OBJECTIVE: Preeclampsia is associated with a higher maternal blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and lower levels of placental growth factor (PlGF) that appear before clinical onset. We aimed to estimate the normal progression of these biomarkers in normal pregnancies and in those affected by preeclampsia. METHODS: We conducted a case-cohort study including low-risk nulliparous women recruited at 11-13 weeks gestation (cohort) and women with preeclampsia (cases). Maternal blood was collected at different points during pregnancy including at the time of diagnosis of preeclampsia for cases. Maternal serum PlGF and sFlt-1 concentrations and the sFlt-1/PlGF ratio were measured using B•R•A•H•M•S plus KRYPTOR automated assays and were compared between patients in both groups matched for gestational age. Cases were stratified as early- (≤34 weeks), intermediate- (35-37 weeks) and late-onset (>37 weeks) preeclampsia. RESULTS: The cohort consisted of 45 women whose results were compared with those of 31 women who developed preeclampsia, diagnosed at a median gestational age of 32 weeks (range 25-38 weeks). We observed that sFlt-1, PlGF and their ratio fluctuated during pregnancy in both groups, with a significant correlation with gestational age after 28 weeks (P < 0.05). We observed a significant difference between cases and controls, with a median ratio 100 times higher in early preeclampsia (P < 0.001), 13 times higher in intermediate preeclampsia (P < 0.001), but no significant difference between groups in late-onset preeclampsia with matched controls. CONCLUSION: PlGF, sFlt-1, and their ratio may be useful in the prediction and diagnosis of early- and intermediate-onset preeclampsia but are not useful for late-onset preeclampsia.