Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome. METHODS: We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076. FINDINGS: Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia. INTERPRETATION: Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction. FUNDING: French Ministry of Health.

Evaluation of the impact of body mass index < 18,5 kg/m2 in early pregnancy on obstetric and neonatal outcomes.

OBJECTIVES: In France, 7% of women have a BMI under 18,5 kg/m2 in early pregnancy. Adverse pregnancy outcomes associated with underweight are rarely described in French literature. This study evaluates obstetric and neonatal outcomes of underweight women compared with women with a normal BMI. METHODS: We conducted a retrospective monocentric study within University hospital of Bicetre. This study included 285 women with singleton pregnancy and a BMI <18.5 kg /m2 who gave birth after 15 weeks of gestation between January 2017 and February 2019. Their socio-demographic characteristics, obstetrical complications, neonatal and postpartum outcomes were compared with those of 285 women with normal BMI. RESULTS: The underweight women are more socially vulnerable and have a significantly higher risk of anemia (p = 0,045) and having small for gestational age infants (p < 0,01). There was no significant difference regarding the mode of delivery and in the early health status of the newborns. Inadequate pregnancy weight gain appeared to be an independent risk factor of low birth weight. CONCLUSION: Our study suggests that a lower-than-normal BMI in early pregnancy is associated with more social difficulties and exposes women to specific morbidity. This is an important element in the initial assessment of obstetrical risk, which justifies an adapted pregnancy follow-up.

Cervical ripening by prostaglandin E2 in patients with a previous cesarean section.

OBJECTIVE: To assess the efficacy and safety of prostaglandin in inducing labor in pregnant women with one previous cesarean section. Secondly, to evaluate predictors of successful vaginal delivery in cervical ripening by prostaglandin in these women. STUDY DESIGN: This was an observational, retrospective, single-center study conducted in a type 3 maternity unit at Bicêtre University Hospital between January 1, 2013 and December 31, 2016. Patients with one previous cesarean section, a singleton pregnancy, a fetus in the cephalic presentation with a medical indication for induction of labor and an unfavorable cervix (Bishop score less than 6) were included in the study. Cervical ripening was performed using a dinoprostone intravaginal device for a duration of 24 h. RESULTS: A total of 153 patients were included in the study. The rate of vaginal delivery was 55.6 % (85/153) overall and 78.3 % (36/46) in the subgroup of 46 women with a previous vaginal delivery before or after the cesarean section. There was no difference in neonatal and maternal morbidity (defined by intraoperative wounds or postpartum hemorrhage or uterine rupture) and mortality between women who delivered vaginally and women who had a cesarean section. The two cases of complete uterine rupture have been reported for patients whose labor was induced by intravaginal prostaglandin followed by intravenous oxytocin. The total maternal morbidity rate was 11.8 % (n = 8/68) in the case of emergency cesarean section. Predictors of vaginal delivery were a history of vaginal delivery, the onset of labor following cervical ripening, and a higher Bishop score before and after the 24 h following the cervical ripening. CONCLUSION: Cervical ripening by prostaglandin after previous cesarean delivery has a 56 % success rate, with a 1.3 % risk of uterine rupture, especially when prostaglandin is combined with oxytocin. Low-risk patients should be identified to propose cervical ripening by prostaglandin.

Two separate placental masses on ultrasound do not always indicate a dichorionic pregnancy.

Monochorionic pregnancies are associated with a higher risk of perinatal morbidity and mortality than dichorionic pregnancies. Early determination of chorionicity by an ultrasound exam between 11+0 and 14+0 weeks' gestation (WG) is essential for the subsequent management of twin pregnancies. The presence of the T-sign is the most specific sign for determination of monochorionicity. During the second trimester, the presence of two distinct placental masses has a lower specificity in determining the chorionicity. We report here two cases of a monochorionic pregnancy with a bipartite placenta, suggesting that a placenta with two separate masses, each with a distinct cord insertion is not always indicative of a dichorionic pregnancy.'

Performance of cervical phIGFBP-1 test alone or combined with short cervical length to predict spontaneous preterm birth in symptomatic women.

We aimed to assess the accuracy of cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) test alone or in combination with cervical length (CL), to predict preterm birth (PTB) in symptomatic women. We performed a prospective cohort study from 2012 to 2015 including singleton pregnancies with symptoms of preterm labor, intact membranes and CL < 25 mm at 24-34 weeks of gestation. Studied outcome were spontaneous delivery within 7 and 14 days of testing and spontaneous PTB at <34 and <37 weeks of gestation. Among 180 women, 21 (11.7%) had a positive phIGFBP-1 test. Spontaneous PTB occurred within 7 days, 14 days of testing and before 34 weeks and 37 weeks in 7.8%, 10.6%, 12.9% and 28.8%, respectively. The phIGFBP-1 test had a low predictive performance for all studied outcomes varying for positive likelihood ratios (2.8 to 3.4) and negative likelihood ratios (0.8). Combining phIGFBP-1 and CL did not increase its predictive ability. After adjustment, positive phIGFBP-1 test was no more independently associated with a delivery within 7 days (p = 0.55), unlike CL < 15 mm (p = 0.04). In conclusion, phIGFBP-1 test alone or in combination with CL has a low predictive accuracy to predict PTB in symptomatic women.

Fertility and pregnancy outcomes after transvaginal cervico-isthmic cerclage.

INTRODUCTION: Prematurity is the leading cause of neonatal morbidity and mortality. Cervical insufficiency seems to be the main risk factor. Treatment is cervical cerclage. In case of failure, a cervico-isthmic cerclage by Fernandez' technique, with the placement of a polypropylene sling by vaginal approach during the first trimester of pregnancy, has proven its effectiveness. The aim of our study is to report effectiveness of Fernandez' cervico-isthmic cerclage in subsequent pregnancies. MATERIALS AND METHODS: This retrospective study, was conducted from March 2002 to April 2014 in the gynecologic department of two teaching hospitals. The inclusion criterion was history of cervico-isthmic cerclage using Fernandez's technique during the previous pregnancy. This study received IRB approval number CEROG 2016-GYN-0302. RESULTS: 125 women underwent a definitive cervico-isthmic cerclage. The total percentage of neonatal survival after 14 weeks was 91% and the total percentage of neonatal survival after 24 weeks of gestation was 98.2%. Out of 114 women, 33 desired a second pregnancy. Out of which 29 had a spontaneous pregnancy. The percentage of total neonatal survival rate after 14 weeks was 92.86% and the percentage of total neonatal survival after 24 weeks was 96.3%. Out of the 29 women with a second pregnancy, 5 women achieved a third pregnancy. The five births occurred after 37 weeks of gestation with a percentage of total neonatal survival of 100%. CONCLUSION: The cervico isthmic cerclage using the technique of Fernandez makes it possible to obtain subsequent pregnancies without further surgery with very satisfactory results regarding neonatal survival.

Bipolar hysteroscopic procedures and placement of Essure microinserts for tubal sterilization: a case control study.

OBJECTIVE: To assess the effectiveness and complication rate with Essure microinsert placements for tubal sterilization and the concomitant bipolar intrauterine surgical procedure. DESIGN: Case control study. SETTING: Department of gynecology and obstetrics of a general hospital in France. PATIENT(S): 382 women, including 41 undergoing one or several concomitant uterine procedures with Essure placement, and 341 undergoing Essure placement only (controls). INTERVENTION(S): Essure placement with or without bipolar hysteroscopic procedure for polyp, myoma, or endometrial ablation. MAIN OUTCOME MEASURE(S): Success rate for microinsert placement and complications at 3 months. RESULT(S): Forty-one patients had Essure microinserts placed in combination with a bipolar hysteroscopic procedure: endometrial resection (n=32), fibroma resection (n=4), or polyp ablation (n=5). They were compared with 341 patients who underwent Essure placement only. The success rate for Essure placement was 97.6% in the combination group versus 97.6% in the control group. The complication rate was 4.9% (n=2) in the combination group versus 2.6% (n=9) in the control group. The difference in the success and complication rates was not statistically significant. CONCLUSION(S): Performing intrauterine bipolar resection during hysteroscopy for sterilization is possible without reducing the Essure placement success rate and without increasing morbidity.