Marie Victoire Senat

Induction of labour versus expectant management for large-for-date fetuses: a randomised controlled trial

BACKGROUNDnMacrosomic fetuses are at increased risk of shoulder dystocia. We aimed to compare induction of labour with expectant management for large-for-date fetuses for prevention of shoulder dystocia and other neonatal and maternal morbidity associated with macrosomia.nnnMETHODSnWe did this pragmatic, randomised controlled trial between Oct 1, 2002, and Jan 1, 2009, in 19 tertiary-care centres in France, Switzerland, and Belgium. Women with singleton fetuses whose estimated weight exceeded the 95th percentile, were randomly assigned (1:1), via computer-generated permuted-block randomisation (block size of four to eight) to receive induction of labour within 3 days between 37(+0) weeks and 38(+6) weeks of gestation, or expectant management. Randomisation was stratified by centre. Participants and caregivers were not masked to group assignment. Our primary outcome was a composite of clinically significant shoulder dystocia, fracture of the clavicle, brachial plexus injury, intracranial haemorrhage, or death. We did analyses by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00190320.nnnFINDINGSnWe randomly assigned 409 women to the induction group and 413 women to the expectant management group, of whom 407 women and 411 women, respectively, were included in the final analysis. Mean birthweight was 3831 g (SD 324) in the induction group and 4118 g (392) in the expectant group. Induction of labour significantly reduced the risk of shoulder dystocia or associated morbidity (n=8) compared with expectant management (n=25; relative risk [RR] 0·32, 95% CI 0·15-0·71; p=0·004). We recorded no brachial plexus injuries, intracranial haemorrhages, or perinatal deaths. The likelihood of spontaneous vaginal delivery was higher in women in the induction group than in those in the expectant management group (RR 1·14, 95% CI 1·01-1·29). Caesarean delivery and neonatal morbidity did not differ significantly between the groups.nnnINTERPRETATIONnInduction of labour for suspected large-for-date fetuses is associated with a reduced risk of shoulder dystocia and associated morbidity compared with expectant management. Induction of labour does not increase the risk of caesarean delivery and improves the likelihood of spontaneous vaginal delivery. These benefits should be balanced with the effects of early-term induction of labour.nnnFUNDINGnAssistance Publique-Hôpitaux de Paris and the University of Geneva.

Prolonged and post-term pregnancies: guidelines for clinical practice from the French College of Gynecologists and Obstetricians (CNGOF).

The duration of pregnancy varies between 40(+0) and 41(+3) weeks. Conventionally, and essentially arbitrarily, a pregnancy is considered to be prolonged after 41(+0) weeks, but the infant is not considered post-term until 42(+0) weeks (Professional consensus). A term birth thus occurs during the period from 37(+0) to 41(+6) weeks. In France, prolonged pregnancies (≥41(+0)weeks) involve 15-20% of pregnant women, and post-term pregnancies (≥42(+0) weeks) approximately 1%. The frequency of post-term pregnancies is very heterogeneous: in Europe and the United States, it ranges from 0.5% to 10% according to country. In prolonged pregnancies, the cesarean section rate-especially the emergency cesarean rate-is multiplied by approximately 1.5 (grade B). From 37(0-6) to 43(0-6) weeks, the risk of perinatal mortality increases regularly, from 0.7‰ to 5.8‰. Meconium aspiration syndrome is responsible for substantial morbidity and mortality, and its incidence increases regularly between 38(+0) and 42(+6) weeks, from 0.24‰ to 1.42‰ (grade B). Similarly, the risks of neonatal acidosis (grade B), 5-min Apgar scores less than 7 (grade B) and admissions to neonatal intensive care (grade B) increase progressively between 38(+0) and 42(+6) weeks. These risks appear to double for post-term growth-restricted newborns (grade C). Ultrasound dating of the pregnancy makes it possible to reduce the risk that it will be incorrectly considered prolonged and that labor will therefore be induced unnecessarily. To harmonize practices, if the crown-rump length (CRL) is correctly measured (this measurement should be taken between 11(+0) and 13(+6) weeks, when CRL should measure from 45 to 84mm), ultrasound dating based on it should be used to determine the official date pregnancy began, regardless of its difference from the date assumed by the patient or estimated based on the date of the last menstrual period. This rule does not apply to pregnancies by IVF, for which the date pregnancy began is defined by the date of oocyte retrieval (Professional consensus). From 37(0-6) to 43(0-6) weeks, the risk of perinatal mortality increases regularly and there is no threshold at which a clear increase in perinatal mortality becomes visible. Fetal monitoring by cardiotocography (CTG) that begins at 41(+0) weeks would cover approximately 20% of women and reduce perinatal morbidity compared with monitoring that begins at 42(+0) weeks (grade C). The frequency recommended for this monitoring ranges between two and three times a week (Professional consensus). For ultrasonography assessment, measurement of the largest fluid pocket is recommended, because measurement of the amniotic fluid index (that is, the sum of the four quadrants) is accompanied by more diagnoses of oligohydramnios, inductions of labor, and cesareans for fetal distress without any improvement in neonatal prognosis (grade A). The practice of assessing the Manning biophysical score increases the number of diagnoses of oligohydramnios and fetal heart rage (FHR) abnormalities and generates an increase in the rates of inductions and cesareans without improving neonatal prognosis. The use of this biophysical score in monitoring prolonged pregnancies is therefore not recommended (grade B). In the absence of a specific disorder, induction of labor can be proposed in patients between 41(+0) and 42(+6) weeks (grade B). Nonetheless, the choice of prolongation beyond above 42(+0) weeks appears to involve an increase in fetal risk, which must be explained to the patient and balanced against the potential disadvantages of induction (Professional consensus). Stripping the membranes can reduce the duration of pregnancy by increasing the number of patients going into labor spontaneously during the week afterward (grade B). Compared to an expectant approach, it does not increase the cesarean section rate (grade A). It reduces recourse to induction by 41% at 41(+0) weeks and by 72% at 42(+0) weeks (grade B), without increasing the risk of either membrane rupture or maternal or neonatal infection (grade B). Used as a tampon or vaginal gel, prostaglandins E2 (PGE2) are an effective method of inducing labor (grade A). They can be used to induce labor successfully, regardless of cervical ripeness (grade A). If misoprostol is chosen, the lowest dose is to be preferred, starting with a vaginal dose of 25μg every 3-6h (grade A). For misoprostol, more powerful studies remain necessary for better defining the doses, routes of administration, tolerance and indications. Misoprostol at any dose is contraindicated in women with uterine scars (grade B). Placement of an intracervical Foley catheter is an effective mechanical means of inducing labor, with less uterine hyperstimulation than prostaglandins and no increase in the cesarean section rate (grade A). Nonetheless, as the risk of infection might be increased, this technique requires more robust evaluation before entering general practice (grade B). In cases of meconium-stained amniotic fluid, pharyngeal aspiration before delivery of the shoulders is not recommended (grade A). The team managing a post-term newborn with meconium-stained amniotic fluid at birth must know how to perform intubation and, if the intubation is not helpful, endotracheal aspiration (grade C) and ventilation with a mask. Routine endotracheal intubation of a vigorous newborn is not recommended (grade A).

Balloon replacement of fetal membranes to facilitate emergency cervical cerclage

BACKGROUND Emergency cerclage can be used in cases of cervical incompetence, even when fetal membranes bulge through the dilated cervix. To facilitate the procedure we used a balloon device to replace the fetal membranes. TECHNIQUE With the patient in a steep Trendelenburg position, after epidural anesthesia, the fetal membranes were replaced into the uterine cavity with an inflated balloon of the type used for endoscopic preperitoneal dissection. Cervical cerclage was done by the McDonald technique. EXPERIENCE We have done 25 emergency cerclages with this technique. The following maternal and perinatal outcomes were assessed retrospectively: age, medical history, gestational age at inclusion and delivery, cervical dilatation at admission, preterm rupture of membranes, clinical or histologic chorioamnionitis, birth weight, admission to the neonatal intensive care unit, neonatal death, and postnatal course. CONCLUSION Replacing prolapsed fetal membranes with an inflated balloon is a convenient technique that allows gestation to be prolonged for an average of 31 days. Cerclage was feasible when the cervix was widely dilated (more than 4 cm); it was associated with prolongation of gestation by a median of 9 days.

Loss of function mutations in EPHB4 are responsible for vein of Galen aneurysmal malformation

See Meschia (doi:10.1093/brain/awy066) for a scientific commentary on this article.Vein of Galen aneurysmal malformation is a congenital anomaly of the cerebral vasculature representing 30% of all paediatric vascular malformations. We conducted whole exome sequencing in 19 unrelated patients presenting this malformation and subsequently screened candidate genes in a cohort of 32 additional patients using either targeted exome or Sanger sequencing. In a cohort of 51 patients, we found five affected individuals with heterozygous mutations in EPHB4 including de novo frameshift (p.His191Alafs*32) or inherited deleterious splice or missense mutations predicted to be pathogenic by in silico tools. Knockdown of ephb4 in zebrafish embryos leads to specific anomalies of dorsal cranial vessels including the dorsal longitudinal vein, which is the orthologue of the median prosencephalic vein and the embryonic precursor of the vein of Galen. This model allowed us to investigate EPHB4 loss-of-function mutations in this disease by the ability to rescue the brain vascular defect in knockdown zebrafish co-injected with wild-type, but not truncated EPHB4, mimicking the p.His191Alafs mutation. Our data showed that in both species, loss of function mutations of EPHB4 result in specific and similar brain vascular development anomalies. Recently, EPHB4 germline mutations have been reported in non-immune hydrops fetalis and in cutaneous capillary malformation-arteriovenous malformation. Here, we show that EPHB4 mutations are also responsible for vein of Galen aneurysmal malformation, indicating that heterozygous germline mutations of EPHB4 result in a large clinical spectrum. The identification of EPHB4 pathogenic mutations in patients presenting capillary malformation or vein of Galen aneurysmal malformation should lead to careful follow-up of pregnancy of carriers for early detection of anomaly of the cerebral vasculature in order to propose optimal neonatal care. Endovascular embolization indeed greatly improved the prognosis of patients.

Impact of routine transvaginal ultrasound monitoring of cervical length in twins on administration of antenatal corticosteroids.

Abstract Objective: To evaluate whether routine measurement of cervical length (CL) by transvaginal ultrasound (TVU) in twin pregnancies can enable identification of women who will give birth before 34 weeks and require antenatal corticosteroids (ACSs), and whether it can limit their administration to women who will give birth later. Study design: Retrospective comparative study in two tertiary referral centers in France. Women with twin gestations followed in two tertiary university hospital maternity units and who delivered from January 1, 2007 to December 31, 2009 were included. In one center, TVU was targeted to women with cases of suspected preterm labor, while the other center used it monthly for all twin pregnancies. The main outcome measure was the administration of a full course of ACS to twins delivered before 34 weeks. Results: Two hundred and seventy women were eligible in the “targeted use” group, and 296 women in the “routine use” group. The rate of administration of at least one full course of ACS for twins born before 34 weeks did not differ between the two groups (85.0% in the targeted use group and 90.0% in the routine use group, P=0.40), but the rate of such administration for those born after 34 weeks was lower in the targeted use group (25.7% vs. 81.2%, P<0.01). On adjusting for confounders using logistic regression modeling, no significant difference in ACS administration before 34 weeks was found between the two groups [adjusted odds ratio (aOR), 0.71, 95% confidence interval (CI), 0.39–1.30]. Conclusion: Routine monitoring performed every month of CL with TVU does not affect the rate of administration of ACS to twins born before 34 weeks, but is associated with a higher rate of such administration for those born later in the specific center of the study.

Le Comité d'éthique de la recherche en obstétrique et gynécologie (CEROG)

OBJECTIVEnTo report the rules and the activity of the institutional review board of the French college of obstetricians and gynecologists (Comité déthique de la recherche en obstétrique et gynécologie [CEROG]) created in 2008. The submission requirements are also described.nnnMETHODSnRetrospective study.nnnRESULTSnThe Ethical Review Committee [institutional review board of the French college of obstetricians and gynecologists (CNGOF)] CEROG have examined 65 project studies in 2008. The median number of submitted studies was 5.5 per month (IQR: 3.75-6.25). The origins of the submission were as follows: tertiary care university hospitals (n=63, 97 %), Inserm (n=1), INRA (n=1). Researches were found to be in conformity with the French laws and regulations, to conform to generally accepted scientific principles and medical research ethical standards in 44 cases (68 %). In 13 cases (20 %), the study has been forwarded to the Persons Protection Committee (PPC) since it concerned biomedical research or usual care research (soin courant). In six cases (9 %), the investigators have not responded to IRB suggestions. In two cases (3 %), the information form has been judged unsatisfactory.nnnCONCLUSIONnThe CEROG is the first national IRB in obstetrics and gynecology. This new committee clarifies IRB submission procedure in France concerning non-interventional studies in the field of obstetrics and gynecology.