Impact of discontinuing oxytocin in active labour on neonatal morbidity: an open-label, multicentre, randomised trial.

BACKGROUND: Oxytocin is effective in reducing labour duration but can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the treatment during labour. We aimed to assess the impact of discontinuing oxytocin during active labour on neonatal morbidity. METHODS: STOPOXY was a multicentre, randomised, open-label, controlled, superiority trial conducted in 21 maternity units in France. Participants who received oxytocin before 4 cm dilation were randomly assigned 1:1 to either discontinuous oxytocin (oxytocin infusion stopped beyond a cervical dilation equal to or greater than 6 cm) or continuous oxytocin (administration of oxytocin continued until delivery). Randomisation was stratified by centre and parity. The primary outcome, neonatal morbidity, was assessed at birth using a composite variable defined by an umbilical arterial pH at birth less than 7·10, a base excess greater than 10 mmol/L, umbilical arterial lactates greater than 7 mmol/L, a 5-min Apgar score less than 7, or admission to the neonatal intensive care unit. Efficacy and safety was assessed in participants who were randomly assigned (excluding those who withdrew consent or were deemed ineligible after randomisation) and had reached a cervical dilation of at least 6 cm. This trial is registered with ClinicalTrials.gov, NCT03991091. FINDINGS: Of 2459 participants randomly assigned between Jan 13, 2020, and Jan 24, 2022, 2170 were eligible to receive the intervention and were included in the final modified intention-to-treat analysis. The primary outcome occurred for 102 (9·6%) of 1067 participants (95% CI 7·9 to 11·5) in the discontinuous oxytocin group and for 101 (9·2%) of 1103 participants (7·6 to 11·0) in the continuous oxytocin group; absolute difference 0·4% (95% CI -2·1 to 2·9); relative risk 1·0 (95% CI 0·8 to 1·4). There were no clinically significant differences in adverse events between the two groups of the safety population. INTERPRETATION: Among participants receiving oxytocin in early labour, discontinuing oxytocin when the active phase is reached does not clinically or statistically significantly reduce neonatal morbidity compared with continuous oxytocin. FUNDING: French Ministry of Health and the Département de la Recherche Clinique et du Développement de l'Assistance Publique-Hôpitaux de Paris.

Association between marked fetal heart rate variability and neonatal acidosis: A prospective cohort study.

OBJECTIVE: To assess the association between marked variability in fetal heart rate (FHR) and neonatal acidosis. DESIGN: Bicentric prospective cohort study. SETTING: From January 2019 to December 2019, in two French tertiary care maternity units. POPULATION: Women in labour at ≥37 weeks of gestation, with continuous FHR monitoring until delivery and with the availability of umbilical arterial pH. Women with intrauterine fetal death or medical termination, multiple pregnancies, non-cephalic presentation or planned caesarean delivery were excluded. METHODS: The exposure was marked variability in FHR in the 60 minutes before delivery, defined as a variability greater than 25 beats per minute, with a minimum duration of 1 minute. To assess the association between marked variability and neonatal acidosis, we used multivariable modified Poisson regression modelling. We then conducted subgroup analyses according to the US National Institute of Child Health and Human Development (NICHD) category of the associated fetal heart rate. MAIN OUTCOME MEASURES: Neonatal acidosis, defined as an umbilical artery pH of ≤7.10. RESULTS: Among the 4394 women included, 177 (4%) had marked variability in fetal heart rate in the 60 minutes before delivery. Acidosis occurred in 6.0% (265/4394) of the neonates. In the multivariable analysis, marked variability was significantly associated with neonatal acidosis (aRR 2.30, 95% CI 1.53-3.44). In subgroup analyses, the association between marked variability and neonatal acidosis remained significant in NICHD category-I and category-II groups. CONCLUSIONS: Marked variability was associated with a twofold increased risk of neonatal acidosis.

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.

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..

Oxidative stress, lipid peroxidation and premature placental senescence in preeclampsia.

Accelerated placental senescence is associated with preeclampsia (PE) and other pregnancy complications. It is characterized by an accelerated decline in placental function due to the accumulation of senescence patterns such as telomere shortening, mitochondrial dysfunction, oxidative damages, increased expression of phosphorylated (serine-139) histone γ-H2AX, a sensitive marker of double-stranded DNA breaks, accumulation of cross-linked ubiquitinated proteins and sirtuin inhibition. Among the lipid oxidation products generated by the peroxidation of polyunsaturated fatty acids, aldehydes such as acrolein, 4-hydroxy-2-nonenal, 4-oxo-2-nonenal, are present in the blood and placenta from PE-affected women and could contribute to PE pathogenesis and accelerated placental aging. In this review we summarize the current knowledge on premature placental senescence and the role of oxidative stress and lipid oxidation-derived aldehydes in this process, as well as their links with PE pathogenesis. The interest of developing (or not) new therapeutic strategies targeting lipid peroxidation is discussed, the objective being a better understanding of accelerated placental aging in PE pathophysiology, and the prevention of PE bad outcomes.

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.

Evaluation of the Prognostic Value of the sFlt-1/PlGF Ratio in Early-Onset Preeclampsia.

OBJECTIVE: Increased expression of soluble fms-like tyrosine kinase 1 (sFlt-1), associated with a decrease in placental growth factor (PlGF), plays a key role in the pathogenesis of preeclampsia (PE). We evaluated the prognostic value of the sFlt-1/PlGF ratio for the onset of adverse maternofetal outcomes (AMFO) in case of early-onset PE with attempted expectant management. STUDY DESIGN: From October 2016 through November 2018, all singleton pregnancies complicated by early-onset PE (before 34 weeks of gestation) were included in a cohort study. The plasma levels of sFlt-1 and PlGF were blindly measured on admission. For the statistical analysis, we performed a bivariate analysis, a comparison of the receiving operating characteristic curves and a survival analysis estimated by the Kaplan-Meier method. RESULTS: Among 109 early PE, AMFO occurred in 87 pregnancies (79.8%), mainly hemolysis, elevated liver enzymes, and low platelet count syndrome and severe fetal heart rate abnormalities requiring urgent delivery. The area under the curve (AUC) of sFlt-1/PlGF ratio was 0.82 (95% confidence interval [CI]: 0.73-0.88) for the risk of AMFO and the difference between the AUCs was significant for each separate standard parameter (p = 0.018 for initial diastolic blood pressure, p = 0.013 for alanine aminotransferase, p < 0.001 for uric acid). Pregnancies were best classified by a cutoff ratio of 293, with a sensitivity of 95% and a specificity of 50%. With a ratio value less than 293, no pregnancy was complicated or had been stopped during the first 5 days. A ratio more than 293 was associated with an increased risk of AMFO onset (hazard ratio [HR]: 3.61; 95% CI: 2.13-6.10; p < 0.001) and had a significant association with the length of time between the diagnosis of PE and delivery (HR: 2.49; 95% CI: 1.56-3.96; p < 0.001). CONCLUSION: The sFlt-1/PlGF ratio is an additional tool in the prediction of AMFO in proven early-onset PE, which is likely to improve care by anticipating severe complications. KEY POINTS: · The sFlt-1/PlGF ratio is associated with AMFO.. · It is an additional tool for physician.. · We proposed a 293 cutoff value for the ratio..

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..

Aspirin for prevention of preeclampsia and fetal growth restriction.

For the past decades, growing attention has been given to aspirin use during pregnancy. It favors placentation by its proangiogenic, antithrombotic, and anti-inflammatory effects. Therefore, low doses of aspirin are prescribed in the prevention of placenta-mediated complications, mainly preeclampsia and fetal growth restriction. However, questions regarding its clinical application are still debated. Aspirin is effective in preventing preeclampsia in a high-risk population. Most guidelines recommend that risk stratification should rely on medical history. Nevertheless, screening performances dramatically improve if biochemical and biophysical markers are included. Concerning the appropriate timing and dose, latest studies suggest aspirin should be started before 16 weeks of pregnancy and at a daily dose of 100 mg or more. Further studies are needed to improve the identification of patients likely to benefit from prophylactic aspirin. Besides, the role of aspirin in the prevention of fetal growth restriction is still questioned.

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.

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.

Perioperative outcomes using LigaSure compared with conventional technique in peripartum hysterectomy.

OBJECTIVE: To evaluate the use of new bipolar vessel sealing system like LigaSure™ compared to the standard surgical technique (suture) during emergency peripartum hysterectomy (EPH). METHODS: A retrospective observational bicentric study was conducted from February 2005 to August 2018 in the maternity wards of the University Hospital of Toulouse and Angers. All EPHs performed up to 24 h after delivery were included. The main outcome was the total blood loss. Secondary outcomes were operating time, number of blood transfusions, per and postoperative complications. A subgroup analysis was performed between hysterectomies performed in emergency and scheduled hysterectomies. RESULTS: Among 111,266 deliveries, 86 women (0.07%) underwent EPH, 29 were operated upon with LigaSure™, 57 with the traditional technique. In the LigaSure™ arm, there were statistically lower blood loss (3198 mL vs 4223 mL, p = 0.02), fewer blood transfusions (62.1% vs 94.7%, p = 0.0003, confirmed in subgroup analysis), and fewer perioperative complications (8.3% vs 45.5%, p = 0.04) for scheduled hysterectomies. CONCLUSION: Bipolar vessel sealing systems such as LigaSure™ are a surgical instrument, easy to use for the surgeon, with an interest in the management of EPH, particularly for total blood loss, transfusions, and intraoperative complications.

Spatulas for entrapment of the after-coming head during vaginal breech delivery.

PURPOSE: To evaluate spatulas for entrapment of the after-coming head (EAH) during vaginal breech delivery, in the setting of failed usual manoeuvres (Bracht or Mauriceau). METHODS: We led a retrospective cohort study in two tertiary referral hospital in France. From 2003 to 2018, we included all deliveries of live children requiring the use of spatulas (Thierry's and Teissier's) for EAH during vaginal breech delivery. RESULTS: Over the period, 59 breech deliveries with spatulas for EAH were enrolled (prevalence 2.3%). No vaginal delivery failures were found. The average term was 36 weeks of gestation. Mean maternal age was 29.4 years and median parity was 1. 50.8% of the foetuses presented as complete breech, 40.7% as frank breech, and 8.5% as footling breech. Maternal morbidity was low: no obstetrical lesions of the anal sphincter, 28% episiotomy (performed before application of instruments in most cases). There was no evidence of foetal over-morbidity. The average weight of the foetuses was 2635g. There was no serious trauma associated with the use of spatulas: only one case of skin lesion and a case of non-severe cephalhematoma could be attributed to the instrument. Mean arterial pH was 7.19, the median 5-min Apgar score was 10. CONCLUSION: In compliance with obstetrical mechanics, spatulas should be considered as an effective instrument during EAH with maternal and foetal safety. This is the first cohort describing the use of an instrument to manage EAH during vaginal breech delivery, while knowledge and mastery of this technique are essential to manage this situation.

Can early ßhCG change and baseline progesterone level predict treatment outcome in patients receiving single dose Methotrexate protocol for tubal ectopic pregnancy?

INTRODUCTION: We aimed to assess the prognostic significance of early ßhCG change and baseline progesterone level on treatment outcome among women receiving single dose Methotrexate protocol for tubal ectopic pregnancy (EP). MATERIAL AND METHODS: Retrospective study involving all consecutive patients diagnosed with EP and receiving Methotrexate therapy form January 2015 to December 2016. Patients were stratified into 2 groups according to treatment outcome: success group (n = 66) involved women who displayed complete resolution of serum ßhCG levels following a single course of Methotrexate; failure group (n = 55) included patients who required repeated Methotrexate administration and/or surgical management. Predictive performances of baseline progesterone and ratio"ßhCG level on day 4/ ßhCG level on day 1″ (d4/d1) on treatment outcome were assessed using Receiving Operating Characteristics curves. RESULTS: The ratio d4/d1 displayed good performances in predicting treatment outcome (AUC = 0.826). A ratio ≤ 0.7 was associated with a success rate of 94% after 1 course of Methotrexate and 100% after 2 courses. In contrast, a ratio >1.7 was associated with a failure rate of 100%. Conversely, baseline progesterone showed poor performances (AUC = 0.611). CONCLUSIONS: Patients with extreme ßhCG changes (n = 33) on day 4 might benefit from a more personalized approach: simplified monitoring in those with a decline ≥30%, anticipated second course of treatment in those with an increase > 70%.