Non-invasive cell-free DNA prenatal screening for trisomy 21 as part of primary screening strategy in twin pregnancies.

OBJECTIVES: The performance of non-invasive prenatal screening using cell-free DNA testing in maternal blood in twin pregnancies is still under-evaluated, while serum marker-based strategies yield poor results. This study aims at assessing the performance of non-invasive prenatal screening for trisomy 21 in twin pregnancies as a first-tier test. The secondary objectives were to assess the failure rate and associated factors. METHODS: This retrospective cohort study included twin pregnancies for which non-invasive prenatal screening using cell-free DNA was performed as the primary screening strategy between May 2017 and October 2019. We used the NIPT VeriSeq® test for in vitro diagnosis and set a fetal fraction cut-off of 4% for monochorionic pregnancies and 8% for dichorionic ones. Clinical data and pregnancy outcome was collected from either physicians or midwives through a questionnaire or were retrieved directly on site. We calculated the performance of non-invasive cell free DNA screening for trisomy 21 and analyzed failure rate and factors. RESULTS: We included 2577 multiple pregnancies among which 1885 (84.8%) were retained after excluding vanishing twins and pregnancies without follow-up. Overall, there were six confirmed trisomy 21 cases (0.32%). For trisomy 21, sensitivity was 100% (95% CI, 61-100%) and the false-positive rate 0.2% (95% CI, 0.07-0.6%). The primary failure rate was 4.6% with 4% due to insufficient fetal fraction. After a new blood draw (59.8% of failed cases), failure rate was only 1.5%. Body mass index and chorionicity were significantly correlated with the risk of failure. CONCLUSION: This study adds further evidence on the high performance of NIPS in twins, as part of the primary screening strategy for trisomy 21, at an extremely low false-positive rate. This article is protected by copyright. All rights reserved.

Clinical profiles of placenta accreta spectrum: the PACCRETA population-based study.

OBJECTIVE: To describe and compare the characteristics of women with placenta accreta spectrum (PAS) and their pregnancy outcomes according to the presence of placenta praevia and a prior caesarean section. DESIGN: Prospective population-based study. SETTING: All 176 maternity hospitals of eight French regions. POPULATION: Two hundred and forty-nine women with PAS, from a source population of 520 114 deliveries. METHODS: Women with PAS were classified into two risk-profile groups, with or without the high-risk combination of placenta praevia (or an anterior low-lying placenta) and at least one prior caesarean. These two groups were described and compared. MAIN OUTCOME MEASURES: Population-based incidence of PAS, characteristics of women, pregnancies, deliveries and pregnancy outcomes. RESULTS: The PAS population-based incidence was 4.8/10 000 (95% CI 4.2-5.4/10 000). After exclusion of women lost to follow up from the analysis, the group with placenta praevia and a prior caesarean included 115 (48%) women and the group without this combination included 127 (52%). In the group with both factors, PAS was more often suspected antenatally (77% versus 17%; P < 0.001) and more often percreta (38% versus 5%; P < 0.001). This group also had more hysterectomies (53% versus 21%, P < 0.001) and higher rates of blood product transfusions, maternal complications, preterm births and neonatal intensive care unit admissions. Sensitivity analysis showed similar results after exclusion of women who delivered vaginally. CONCLUSION: More than half the cases of PAS occurred in women without the combination of placenta praevia and a prior caesarean delivery, and these women had better maternal and neonatal outcomes. We cannot completely rule out that some of the women who delivered vaginally had placental retention rather than PAS; however, we found similar results among women who delivered by caesarean. TWEETABLE ABSTRACT: Half the women with PAS do not have both placenta praevia and a prior caesarean delivery, and they have better maternal outcomes.

Initially untreated fasting hyperglycaemia in early pregnancy: prognosis according to occurrence of gestational diabetes mellitus after 22 weeks' gestation: a case-control study.

AIMS: To evaluate the percentage of women with untreated fasting hyperglycaemia in early pregnancy who develop gestational diabetes mellitus after 22 weeks' gestation, the determinants of gestational diabetes development in such women and the prognosis of early fasting hyperglycaemia according to whether the women go on to develop gestational diabetes. METHODS: From a large cohort of women who delivered in our hospital between 2012 and 2016, we retrospectively selected all those who had untreated early fasting hyperglycaemia and separated them into a 'gestational diabetes' and a 'no-gestational diabetes' group according to oral glucose tolerance test results after 22 weeks' gestation. We compared the incidence of a predefined composite outcome (preeclampsia or large-for-gestational-age infant or shoulder dystocia or neonatal hypoglycaemia) in both groups. RESULTS: A total of 268 women (mean fasting plasma glucose 5.3 ± 0.3 mmol/l at a mean ± sd of 10.2 ± 4.2 weeks' gestation) were included. Gestational diabetes developed in 134 women and was independently associated with early fasting plasma glucose ≥ 5.5 mmol/l [odds ratio 3.16 (95% CI 1.57, 6.33)], age ≥ 30 years [odds ratio 2.78 (95% CI 1.46, 5.31)], preconception obesity [odds ratio 2.12 (95% CI 1.11, 4.02)], family history of diabetes [odds ratio 1.87 (95% CI 1.00, 3.50)] and current employment [odds ratio 0.46 (95% CI 0.26, 0.83)]. Despite treatment, gestational diabetes induced a significant increase in the composite outcome as compared to no gestational diabetes (odds ratio 2.16 [95% CI 1.08, 4.34]). The association disappeared after adjustment for risk factors. CONCLUSIONS: Only half of the women with early fasting hyperglycaemia and no specific care subsequently developed gestational diabetes, and these women had a poor prognosis despite gestational diabetes treatment. Poor prognosis was mostly attributable to risk factors. Our results suggest that only women with certain risk factors should be screened for early fasting hyperglycaemia.

Induction du travail après une version par manœuvres externes pour siège réussie : un sur-risque de césarienne?

OBJECTIVE: To assess the effect of successful external cephalic version (ECV) on the risk of caesarean section (CS) during attempted vaginal delivery after induction of labour. METHODS: A unicentric matched retrospective observational case-control cohort study with exposed and unexposed groups. All pregnant women who had an induction of labour after a successful external cephalic version (sECV) between 1998 and 2016 were included. A total of 88 cases were compared with 176 controls (spontaneous cephalic presentation), matching for the year of delivery, parity, gestational age, indication and mode of induction of labour. The main outcome measure was the risk of caesarean. A univariate analysis and a multivariate logistic regression analysis were performed. RESULTS: The caesarean section rate was significantly higher after sECV (22% versus 13.1%; p = 0.039) especially for postdate pregnancy (55% versus 8.2%; p <0.05). For the univariate analysis, age (31 years and 4 months versus 24 years and 6 months; p <0.01) and maximal speed of oxytocin infusion (72 ml/h versus 68 ml/h; p = 0.04) were higher in the case group. The multivariate analysis showed that the risk of caesarean section was significantly increased after an sECV (aOR 1.946; 95% CI 1.017-3.772) and after the use of prostaglandins for ripening (aOR 1.951; 95% CI 1.097-3.468), and decreased for multipara (aOR 0.208; 95% CI 0.114-0.377). CONCLUSION: Women who have a successful ECV are at increased risk of caesarean section after subsequent induction of labour.

Improving postpartum glucose screening after gestational diabetes mellitus: a cohort study to evaluate the multicentre IMPACT initiative.

AIMS: To evaluate a mobilization campaign, the IMPACT initiative, which included multidisciplinary meetings, provision of information and a systematic prescription of an oral glucose tolerance test to improve the rate of glucose screening in women with gestational diabetes mellitus in the four largest maternity units in our area, starting in March 2011. METHODS: We retrospectively compared the level of self-reported screening during the first 6 months postpartum of women who gave birth after having been diagnosed with gestational diabetes before (January 2009 to December 2010) and after the IMPACT campaign (April 2011 to February 2012). RESULTS: We included 961 women (589 in the period before and 372 in the period after the campaign was initiated) with a mean ± SD age of 33.2 ± 5.3 years and BMI of 27.8 ± 5.3 kg/m². Multivariate analysis, stratified using a propensity score in order to limit bias caused by imbalance between both periods, showed that the postpartum screening rate was higher after the campaign began (48.9 vs 33.3%, odds ratio 1.7, 95% CI 1.1-2.5; P = 0.019) and higher in women who received insulin treatment during pregnancy (odds ratio 2.3, 95% CI 1.5-3.6; P < 0.001), consumed fruit and vegetables daily (odds ratio 1.6, 95% CI 1.1-2.4; P = 0.035) and did not smoke (smoking vs non-smoking: odds ratio 0.3, 95% CI 0.1-0.7; P = 0.01). There was no interaction between the campaign effect and these particular conditions. The proportion of oral glucose tolerance tests performed in women who underwent screening increased from 6.3 to 33.0%. CONCLUSIONS: The IMPACT campaign increased postpartum screening, and the use the oral glucose tolerance test in particular. The effect of this initiative might be reinforced in women who are non-daily consumers of fruit and vegetables, smokers and those who do not receive insulin treatment during pregnancy.

Prognosis associated with initial care of increased fasting glucose in early pregnancy: A retrospective study.

AIM: To evaluate whether the initial care of women with fasting plasma glucose (FPG) levels at 5.1-6.9mmol/L before 22 weeks of gestation (WG), termed 'early fasting hyperglycaemia', is associated with fewer adverse outcomes than no initial care. METHODS: A total of 523 women with early fasting hyperglycaemia were retrospectively selected in our department (2012-2016) and separated into two groups: (i) those who received immediate care (n=255); and (ii) those who did not (n=268), but had an oral glucose tolerance test (OGTT) at or after 22 WG, with subsequent standard care if hyperglycaemia (by WHO criteria) was present. The number of cases of large-for-gestational age (LGA) infants, shoulder dystocia and preeclampsia with initial care of early fasting hyperglycaemia were compared after propensity score modelling and accounting for covariates. RESULTS: Of the 268 women with no initial care, 134 had hyperglycaemia after 22 WG and then received care. Women who received initial care vs those who did not were more likely to be insulin-treated during pregnancy (58.0% vs 20.9%, respectively; P<0.00001), gained less gestational weight (8.6±5.4kg vs 10.8±6.1kg, respectively; P<0.00001), had a lower rate of preeclampsia [1.2% vs 2.6%, respectively; adjusted odds ratio (aOR): 0.247 (0.082-0.759), P=0.01], and similar rates of LGA infants (12.2% vs 11.9%, respectively) and shoulder dystocia (1.6% vs 1.5%, respectively). When initial FPG levels were ≥5.5mmol/L (prespecified group, n=137), there was a lower rate of LGA infants [6.7% vs 16.1%, respectively; aOR: 0.332 (0.122-0.898); P=0.03]. CONCLUSION: Treating women with early fasting hyperglycaemia, especially when FPG is ≥5.5mmol/L, may improve pregnancy outcomes, although this now needs to be confirmed by randomized clinical trials.

Performance of a selective screening strategy for diagnosis of hyperglycaemia in pregnancy as defined by IADPSG/WHO criteria.

AIM: Our study evaluated the performance of a selective screening strategy for hyperglycaemia in pregnancy (HIP) based on the presence of risk factors (RFs; body mass index≥25kg/m2, age≥35years, family history of diabetes, personal history of HIP or macrosomic infant) to diagnose HIP and to predict HIP-related events. METHODS: Women with no known diabetes who had undergone complete universal screening (early, before 22weeks of gestation and, if normal, in the second part of pregnancy) at our department (2012-2016) were selected, resulting in four groups of women according to the presence of HIP and/or RFs, with a predefined composite endpoint (preeclampsia or large-for-gestational-age infant or shoulder dystocia). RESULTS: Included were 4518 women: 23.5% had HIP and 71.1% had at least one RF. The distribution among our four groups was: HIP-/RF- (n=1144); HIP-/RF+ (n=2313); HIP+/RF- (n=163); and HIP+/RF+ (n=898). HIP was more frequent when RFs were present rather than absent (33.1% vs 15.4%, respectively; P<0.001). Incidence of the composite endpoint differed significantly (P<0.0001) across groups [HIP-/RF- 6.3%; HIP-/RF+ 13.2%; HIP+/RF- 8.6%; and HIP+/RF+ 17.1% (HIP effect: P<0.05; RF effect: P<0.001; interaction HIP * RF: P=0.94)] and significantly increased with the number of RFs (no RF: 6.3%, 1 RF: 10.8%, 2 RFs: 14.7%, 3 RFs: 28.0%, 4-5 RFs: 25.0%; P<0.0001). CONCLUSION: RFs are predictive of HIP, although 15.4% of women with HIP have no RFs. Also, irrespective of HIP status, RFs are predictive of HIP-related events, suggesting that overweight/obesity, the only modifiable RFs, could be targets of interventions to improve pregnancy prognosis.

[Pregnancy associated Plasmodium falciparum malaria discovered fortuitously: report of two cases]. / Découverte fortuite de paludisme àPlasmodium falciparum au cours de la grossesse : à propos de deux cas.

We report two cases of pregnancy-associated Plasmodium falciparum malaria discovered fortuitously. These two women were born in Africa and their last visit in an endemic area was more than one year before. It is well known that pregnancy is one of major risks of late onset of P. falciparum malaria. In the two cases reported in this study, clinical signs of malaria were not specific and we will describe the interest to detect more systematically pregnant African women, first arrival immigrants.

[Eclampsia: retrospective study about 16 cases]. / Eclampsie: étude rétrospective de 16 cas.

OBJECTIVE: To determine the etiologic factors, circumstances of diagnosis, obstetrical management and complications of eclampsia and to value the maternal and perinatal outcomes. PATIENTS AND METHODS: We conducted a retrospective descriptive study, from January 1996 to December 2006 in a maternity type IIB. RESULTS: Sixteen cases of eclampsia were studied. The prevalence of eclampsia over the study period was 8.1 per 10,000 births, without annual change in the incidence. The mean age of the patients was 27.8+/-6.7 years. The major risk factor was the primipaternity (87.5%). The eclampsia occurred in ante-, peri- and post-partum in 56, 6 and 38% of the cases, respectively. In cases of eclampsia, 75% of the patients had elevated blood pressure, 93% presented headache, but 62% presented with an atypical form with less than three functional symptoms (headache, visual trouble, hyperreflexia). Various treatments had been started: antihypertensive treatment (75%), antiepileptic treatment (69%) and magnesium sulphate (94%). Eleven patients had developed complications, mainly HELLP syndrome (10 patients). No maternal death was noted. The mean birth weight was 2366+/-818 g, 43.8% of children had birth weight less than the 10th percentile, and 87.5% of children were girls. One fetal and one perinatal death at day 19 had been noted. DISCUSSION AND CONCLUSION: Nowadays, the physiopathology of eclampsia remains misunderstood. It is difficult to establish risk factors, the primipaternity being certainly one of these. Eclampsia may occur in an atypical and unforeseeable form in well followed patients, without risk factor. The diagnosis should be done quickly for an adapted treatment and obstetrical management.

[Use of enfurvitide in pregnancy in HIV positive women in seven cases]. / Utilisation de l'enfuvirtide chez la femme enceinte séropositive VIH, à propos de sept cas.

OBJECTIVE: With a panel of more than 22 drugs, the treatment of HIV subjects is nowadays quite easier. But due to the number of multiparus women often harbouring a multidrug resistant virus, or seen late in pregnancy or inobservant, taking care of these pregnancies remains difficult. The use of enfuvirtide seems quite interesting for these situations. PATIENTS AND METHODS: In a retrospective study, we have focused our work on the consequences of enfuvirtide used in seven pregnancies, paying particular attention to efficacy, pharmacokinetics and tolerance. RESULTS: The use of enfuvirtide during 30 days in average seems safe and the tolerance was satisfactory in all seven cases. All infants are seronegative without abnormalities. The dosages in umbilical cord were negative. Five women experienced an elective caesarean, one had caesarean section in emergency, and one had a vaginal delivery. DISCUSSION AND CONCLUSION: The 23 cases published in the English literature indicate the interest of enfuvirtide use in these difficult situations. Indeed, enfuvirtide is injectable, favouring the adherence; it has a good tolerance, a quick efficacy and no placental transfer. Evidently, enfuvirtide is always prescribed in association.

[Induction of labor in women with previous caesarean delivery with balloon catheter: Is it worth it?] / Déclenchement par ballonnet en cas d'utérus cicatriciel et col défavorable : la tentative en vaut-elle la chandelle ?

OBJECTIF: Balloon catheters for labor induction at term after previous cesarean section is an alternative option to iterative cesarean section. The aim of this study was to analyze the maternal and neonatal outcomes of the trial of labor after cesarean (TOLAC) in women with unfavorable cervix and balloon catheter induction, 2 years after introduction of this process. METHODS: Unicentric observational study of women with term cephalic singleton, unfavorable cervix (simplified Bishop score<5) after TOLAC using double-balloon catheter. Were analyzed the mode of delivery and severe maternal (uterine rupture, post-partum hemorrhage, severe perineal tears) and neonatal (neonatal unit admission, APGAR<7 at 5minutes, pH<7.1) outcomes. Predictive factors for failed TOLAC were analyzed by using multivariate logistic regression. RESULTS: Between 2016-2017, 455 (75.4%) women had TOLAC, whose 59 (13%) women with balloon catheter. The overall vaginal delivery (VD) was 73.9%. After Balloon catheter, the VD rate was 50.8%, versus 79.1% after spontaneous labor, and 68.2% after alone oxytocin/artificial membrane rupture induction (P<0.05). Previous VD (aOR 0.176 CI-95% [0.048-0.651]) and prior sweeping membrane (aOR 0.161 CI-95% [0.034-0.761]) was protective for cesarean section after TOLAC. Severe maternal and neonatal morbidities were observed in 10 (17%) and 8 (13.6%) cases, respectively. CONCLUSION: Double-Balloon catheter is an option for unfavorable cervix and term induction after previous cesarean section. However, the TOLAC in women whose unfavorable cervix is not without maternal and neonatal risk, especially due to its failure.

Is episiotomy worthwile to prevent obstetric anal sphincter injury during operative vaginal delivery in nulliparous women?

OBJECTIVES: Episiotomy is a marker of Obstetric Anal Sphincter Injury (OASIS) condition, therefore, unmeasured factors could have biased the strength of the association between episiotomy and reduced OASIS during Operative Vaginal Delivery (OVD). The aim of this study was to compare the OASIS rate during OVD according to episiotomy practice. STUDY DESIGN: Retrospective cohort study of all nulliparous pregnant women attempting an OVD between 2014-2017. To avoid unmeasured bias, all maternal and delivery data were prospectively captured after the birth. The strong relationship between parity and episiotomy practice (indication bias) lead to analyze only nulliparous women. Association between mediolateral episiotomy and OASIS following OVD was performing by using multivariate logistic regression analysis including significant variable in univariate analysis and relevant factors known to be associated both with OASIS and/or OVD. RESULTS: Over the study period, 1709 (17.1%) women had an OVD, among them 40 (2.3%) had OASIS. In the 1342 (78.5%) nulliparous women, OASIS rate were 2% and 5.1% with and without episiotomy (p < 0.01). In multivariate analysis a lower incidence of OASIS with the use of episiotomy (OR 0.267 IC 0.132-0.541) were observed. The persistent occiput posterior position was associated with an increase risk of OASIS (OR 6.742 IC 2.376-19.124). Spatula/forceps, as compared to vacuum operative vaginal delivery increased the risk OASIS (OR 2.847 IC 1.311-7.168). Area under the curve of the model was 0.745. CONCLUSION: Episiotomy is a modifiable risk factors which can contribute to reduce the risk of OASIS in nulliparous women with operative vaginal delivery. This intervention should be included in a global management of the second stage of labor.

Predicting the likelihood of a live birth for women with endometriosis-related infertility.

OBJECTIVE: Endometriosis affects 10% of women in reproductive age and alters fertility. Its management is still debated notably the timing of surgery and ART in infertility. Several tools have been created to guide the practitioner and the couple yet many limitations persist. The objective is to create a nomogram to predict the likelihood of a live birth after surgery followed by assisted reproductive technology (ART) for patients with endometriosis-related infertility. STUDY DESIGN: All women in a public university hospital who attempted to conceive by ART after surgery for endometriosis-related infertility from 2004 to 2016 were included. We created a model using multivariable linear regression based on a retrospective database. RESULT: Of the 297 women included, 171 (57.6%) obtained a live birth. Age, duration of infertility, number of ICSI-IVF cycles, ovarian reserve and the revised American Fertility Society (rAFS) score were included in the nomogram. The predictive model had an area under the curve (AUC) of 0.77 (95% CI, 0.75-0.79) and was well calibrated. The external validation of the model was achieved with an AUC of 0.71 (95% CI, 0.69-0.73) and calibration was good. The staging accuracy according to AUC criteria for the nomogram compared to the currently used Endometriosis Infertility Index to predict live births were 0.77 (95% CI, 0.75-0.79) and 0.60 (95% CI: 0.57-0.63), respectively. CONCLUSION: This simple tool appears to accurately predict the likelihood of a live birth for a patient undergoing ART after surgery for endometriosis-related infertility. It could be used to counsel patients in their choice between spontaneous versus ART conception, or oocyte donation.

Early screening for gestational diabetes mellitus is not associated with improved pregnancy outcomes: an observational study including 9795 women.

AIMS: In addition to screening for hyperglycaemia during pregnancy after 24 weeks of gestation (WG), the current guidelines also suggest screening in early pregnancy and referring women with early gestational diabetes mellitus (eGDM) or overt diabetes (OD) for immediate care. Our aim was to evaluate this strategy. METHODS: This study evaluated, at our hospital (2012-2016), whether the incidence of a predefined composite outcome (preeclampsia, large-for-gestational-age infant, shoulder dystocia) and secondary outcomes was different when women were screened only after 22WG ('late screening only') or before 22WG and treated for eGDM or OD if present, with repeat screening after 22WG if absent ('early ± late screening'). RESULTS: Early ± late screening (n = 4605, 47.0%) increased between 2012 and 2016 (P < 0.0001) and was associated with more risk factors for GDM than late screening only. Glycaemic status differed in both groups (early ± late screening: eGDM 10.3%, GDM 12.1%, OD 0.9% vs. late screening only: GDM 16.8%, OD 1.2%; P < 0.001), with a higher rate of insulin therapy (8.9% vs. 6.0%; P < 0.001) and less gestational weight gain (11.1 ± 5.4 kg vs. 11.4 ± 5.5 kg; P = 0.013) in the early ± late screening group. Rates of those meeting the composite criterion were similar in both groups [11.6% vs. 12.0%, respectively; odds ratio (OR): 1.040, 95% confidence interval (CI): 0.920-1.176; P = 0.53] and remained comparable after adjusting for Propensity Scores (OR: 1.046, 95% CI: 0.924-1.185; P = 0.4790). Rates for secondary outcomes were also similar in both groups. CONCLUSION: While a strategy including early measurement of fasting plasma glucose during pregnancy increases the incidence and care of hyperglycaemia during pregnancy, it may not significantly improve pregnancy outcomes.

[Chronic histiocytic intervillositis: Diagnosis and management]. / Intervillites chroniques histiocytaires : bilan et prise en charge.

Chronic intervillositis is a rare condition, which is associated with severe obstetrical outcome and high recurrence rate. Obstetrical adverse events are intrauterine growth restriction, recurrent early miscarriages, intrauterine deaths and prematurity by placental insufficiency. The determination of the extension and the intensity of the chronic intervillositis are not currently standardized. High rates of recurrence have been described, but actually there is no reliable predictive biomarker. No treatment is currently validated, but the use of immunomodulatory drugs could be justified by the possible autoimmune or allo-immune origin. The treatment should be particularly discussed in patients with recurrent and severe obstetrical adverse events and in the presence of severe and massive histological lesions.

[Vasa previa: one case]. / Vasa praevia: à propos d'un cas.

Vasa previa is a rare condition (1/2000 to 1/5000) in which the rupture of membranes may result in fetal haemorrhage (Benckiser's haemorrhage). We report one unusual case of delayed Benckiser's haemorrhage 12 hours after rupture of membranes. We point out the risk situations in which prenatal diagnosis should particularly be sought: low-lying placenta at routine second trimester ultrasound screening, bilobate or succenturiate placenta, velamentous insertion of the umbilical cord, in vitro fertilization. A universal screening, as proposed by certain authors, is also discussed.