Norbert Winer

Maternal Outcome After Conservative Treatment of Placenta Accreta

OBJECTIVE: To estimate maternal outcome after conservative management of placenta accreta. METHODS: This retrospective multicenter study sought to include all women treated conservatively for placenta accreta in tertiary university hospital centers in France from 1993 to 2007. Conservative management was defined by the obstetricians decision to leave the placenta in situ, partially or totally, with no attempt to remove it forcibly. The primary outcome was success of conservative treatment, defined by uterine preservation. The secondary outcome was a composite measure of severe maternal morbidity including sepsis, septic shock, peritonitis, uterine necrosis, fistula, injury to adjacent organs, acute pulmonary edema, acute renal failure, deep vein thrombophlebitis or pulmonary embolism, or death. RESULTS: Of the 40 university hospitals that agreed to participate in this study, 25 institutions had used conservative treatment at least once (range 1–46) and had treated a total of 167 women. Conservative treatment was successful for 131 of the women (78.4%, 95% confidence interval [CI] 71.4–84.4%); of the remaining 36 women, 18 had primary hysterectomy and 18 had delayed hysterectomy (10.8% each, 95% CI 6.5–16.5%). Severe maternal morbidity occurred in 10 cases (6.0%, 95% CI 2.9–10.7%). One woman died of myelosuppression and nephrotoxicity related to intraumbilical methotrexate administration. Spontaneous placental resorption occurred in 87 of 116 cases (75.0%, 95% CI 66.1–82.6%), with a median delay from delivery of 13.5 weeks (range 4–60 weeks). CONCLUSION: Conservative treatment for placenta accreta can help women avoid hysterectomy and involves a low rate of severe maternal morbidity in centers with adequate equipment and resources. LEVEL OF EVIDENCE: II

Intrauterine infection induces programmed cell death in rabbit periventricular white matter

An association between chorioamnionitis and periventricular leukomalacia has been reported in human preterm infants. However, whether this link is causal has not been convincingly established, and the underlying molecular mechanisms remain unclear. The objective of this study was to establish a reproducible model of cerebral white matter disease in preterm rabbits after intrauterine infection. Escherichia coli was inoculated into both uterine horns of laparotomized pregnant rabbits when gestation was 80% complete. The fetuses were delivered by cesarean section and killed 12, 24, or 48 h after the inoculation. Programmed cell death in the white matter was evaluated by hematoxylin-eosin-saffron staining and in situ fragmented DNA labeling (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). In a first group of 14 pregnant rabbits not treated with antibiotics, all fetuses delivered 48 h after inoculation were stillborn, whereas fetuses extracted 12 or 24 h after inoculation were alive. No significant cell death was detected in the live fetuses compared with the control noninfected rabbits. In a second group of five pregnant rabbits treated with ceftriaxone initiated 24 h after the inoculation and continued until cesarean section was performed 48 h after inoculation, 13 fetuses were alive, but all showed evidence of extensive programmed cell death in the white matter by hematoxylin-eosin-saffron staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. White matter damage became histologically detectable only 48 h after inoculation. Three of the 13 brains displayed periventricular white matter cysts mimicking human cystic periventricular leukomalacia. The high reproducibility of white matter damage in our model should permit further studies aimed at unraveling the molecular mechanisms of periventricular leukomalacia.

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

BACKGROUND Macrosomic 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. METHODS We 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. FINDINGS We 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. INTERPRETATION Induction 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. FUNDING Assistance Publique-Hôpitaux de Paris and the University of Geneva.

Twin pregnancies: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF)

The rate of twin deliveries in 2008 was 15.6 per 1000 in France, an increase of approximately 80% since the beginning of the 1970s. It is recommended that chorionicity be diagnosed as early as possible in twin pregnancies (Professional Consensus). The most relevant signs (close to 100%) are the number of gestational sacs between 7 and 10 weeks and the presence of a lambda sign between 11 and 14 weeks (Professional Consensus). In twin pregnancies, nuchal translucency is the best parameter for evaluating the risk of aneuploidy (Level B). The routine use of serum markers during the first or the second trimester is not recommended (Professional Consensus). In the case of a choice about sampling methods, chorionic villus sampling is recommended over amniocentesis (Professional Consensus). Monthly follow-up by a gynaecologist-obstetrician in an appropriate facility is recommended for dichorionic pregnancies (Professional Consensus). A monthly ultrasound examination including an estimation of fetal weight and umbilical artery Doppler is recommended (Professional Consensus). It is recommended to plan delivery of uncomplicated dichorionic diamniotic twin pregnancies from 38 weeks and before 40 weeks (Level C). Monthly prenatal consultations and twice-monthly ultrasound are recommended for monochorionic twins (Professional Consensus). It is reasonable to consider delivery from 36 weeks but before 38 weeks+6 days, with intensified monitoring during that time (Professional Consensus). Prenatal care of monochorionic pregnancies must be provided by a physician working in close collaboration with a facility experienced in the management of this type of pregnancy and its complications (Professional Consensus). The increased risk of maternal complications and the high rate of medical interventions justify the immediate and permanent availability of a gynaecologist-obstetrician with experience in the vaginal delivery of twins (Professional Consensus). It is recommended that the maternity ward where delivery takes place have rapid access to blood products (Professional Consensus). Only obstetric history (history of preterm delivery) (Level C) and transvaginal ultrasound measurement of cervical length (Level B) are predictive factors for preterm delivery. No study has shown that the identification by transvaginal sonography (TVS) of a group at risk of preterm delivery makes it possible to reduce the frequency of such deliveries in asymptomatic patients carrying twins (Professional Consensus). It is important to recognize signs of TTTS early to improve the management of these pregnancies (Professional Consensus). Treatment and counseling must be performed in a center that can offer fetoscopic laser coagulation of placental anastomoses (Professional Consensus). This laser treatment is the first-line treatment (Level B). In the absence of complications after laser treatment, planned delivery is recommended from 34 weeks and no later than 37 weeks (Professional Consensus). For delivery, it is desirable for women with a twin pregnancy to have epidural analgesia (Professional Consensus). The studies about the question of mode of delivery have methodological limitations and lack of power. Active management of the delivery of the second twin is recommended to reduce the interval between the births of the two twins (Level C). In the case of non-cephalic presentation, total breech extraction, preceded by internal version manoeuvres if the twins position is transverse, is associated with the lowest cesarean rates for second twins (Level C). In the case of high and not yet engaged cephalic presentation and if the team is appropriately trained, version by internal manoeuvres followed by total breech extraction is to be preferred to a combination of resumption of pushing, oxytocin perfusion, and artificial rupture of the membranes, because the former strategy appears to be associated with fewer cesareans for the second twin (Level C).

Prevention of preterm delivery by 17 alpha-hydroxyprogesterone caproate in asymptomatic twin pregnancies with a short cervix: a randomized controlled trial

OBJECTIVE The objective of the study was to evaluate the use of 17 alpha-hydroxyprogesterone caproate (17P) to reduce preterm delivery in women with a twin pregnancy and short cervix. STUDY DESIGN This open-label, multicenter, randomized controlled trial included women with a twin pregnancy between 24(+0) and 31(+6) weeks of gestation who were asymptomatic and had a cervical length of 25 mm or less measured by routine transvaginal ultrasound. Women were randomized to receive (or not) 500 mg of intramuscular 17P, repeated twice weekly until 36 weeks or preterm delivery. The primary outcome was time from randomization to delivery. Analysis was performed according to the intent-to-treat principle. RESULTS The 17P and control groups did not differ significantly for median [interquartile range] time to delivery: 45 (26-62) and 51 (36-66) days, respectively. However, treatment with 17P was associated with a significant increase in the rate of preterm delivery before 32 weeks. CONCLUSION Twice-weekly injections of 17P did not prolong pregnancy significantly in asymptomatic women with a twin pregnancy and short cervix.

Pseudoamniotic band syndrome: a rare complication of monochorionic twins with fetofetal transfusion syndrome treated by laser coagulation

OBJECTIVE The purpose of this study was to assess the incidence and risk factors of limb constriction defects that are related to pseudoamniotic band syndrome (PABS) after selective fetoscopic laser surgery (FLS) in fetofetal transfusion syndrome (FFTS). STUDY DESIGN All consecutive cases of FFTS that were treated by selective FLS between 1999 and 2006 were examined prospectively for PABS at the time of delivery. Incidence and characteristics of PABS were reported. Univariate analysis was conducted to look for potential risk factors of developing PABS. RESULTS The 438 consecutive FFTS cases were treated at 15-26 weeks of gestation; PABS developed in 8 cases (1.8 %). The affected twin was always the former recipient. The diagnosis was made prenatally in 2 of 8 cases (25%). All cases survived the perinatal period. PABS affected fetal leg, arm, and foot in 3, 4, and 1 cases, respectively. In 5 (62.5%) and 7 (87.5%) cases, PABS occurred after premature rupture of membranes and intrauterine death of the donor, respectively. In 4 cases (50%), there was both premature rupture of membranes (PROM) and intrauterine fetal death; in 3 cases (37.5%), there was intrauterine fetal death alone, and in 1 case (12.5%), there was PROM alone. In the remaining 430 cases, PROM occurred in 62 cases (14.4%) and 66 cases (15.3%) within and after 3 weeks after surgery, respectively. PROM was significantly more frequent within the group that was complicated with PABS than within the rest of the cohort (P = .05). No maternal, fetal, or perioperative risk factor could be identified. CONCLUSION Awareness and targeted serial ultrasound evaluation in this high-risk group may improve prenatal diagnosis, counseling, and management of PABS after FLS.

A score‐based method for quality control of fetal images at routine second‐trimester ultrasound examination

Our aim was to develop and evaluate the feasibility and reproducibility of score‐based quality control for routine standardized fetal ultrasound images obtained in the second trimester of pregnancy.

Obstetrical prognosis for carbon dioxide laser conisation of the uterine cervix

Carbon dioxide laser conisation is a very reliable surgical technique for cervical intraepithelial dysplasia. As cervical morphology and function are better preserved than with other techniques, obstetrical morbidity should be lower in the often young and pauciparous women who undergo this procedure. In our study comparing the course of 71 pregnancies (55 children) in 54 operated women with that of 82 pregnancies (59 children) in these same women before conisation, the rates for complications at the beginning of pregnancy were similar (respectively, 14.1% and 13.4%, early spontaneous abortions; 2.8% and 2.4%, extrauterine pregnancies; and no late spontaneous abortions). The increased risks of premature delivery (13.2% vs. 8.5%), chorioamnionitis (1.9% vs. 0%), premature rupture of membranes (1.9% vs. 0%) and prematurity (11.3% vs. 1.7%) were not statistically significant. Only the percentage of natural term births was significantly reduced (73.6% vs. 90%; P = 0.025), but this difference was no longer apparent after correction for the prevalence of associated obstetrical pathologies and prematurity and/or cesarean factors which was significantly greater for the 53 pregnancies that developed after carbon dioxide laser conisation.

Brachmann–de Lange syndrome: a cause of early symmetric fetal growth delay

Brachmann-de Lange syndrome is characterized by pre- and postnatal growth retardation, microbrachycephaly, hirsutism, various visceral and limb anomalies and a typical face. A sonographic prenatal diagnosis at mid-trimester is reported in a case of severe, symmetrical fetal growth delay at 20 weeks gestation, with a thickened skin on the forehead, a small nose and a marked depressed nasal bridge, a long philtrum, micrognathia and a persistently flexed right forearm, with a single bone associated to oligodactyly. Due to the severe mental impairment with a commonly estimated intelligence quotient under 60, the pregnancy was terminated after parental consent.

Enoxaparin and Aspirin Compared With Aspirin Alone to Prevent Placenta-mediated Pregnancy Complications: A Randomized Controlled Trial

OBJECTIVE: To evaluate whether daily enoxaparin, added to low-dose aspirin, started before 14 weeks of gestation reduces placenta-mediated complications in pregnant women with previous severe preeclampsia diagnosed before 34 weeks of gestation. METHODS: In this open-label multicenter randomized trial, we enrolled consenting pregnant women with previous severe preeclampsia diagnosed before 34 weeks of gestation, gestational age at randomization of 7–13 weeks, singleton pregnancy, and no plan for anticoagulation. Eligible patients were randomly assigned to a one-to-one ratio to receive daily either 4,000 international units enoxaparin plus 100 mg aspirin or 100 mg aspirin alone. Randomization was done by a web-based randomization system. The primary composite outcome comprised maternal death, perinatal death, preeclampsia, small for gestational age (less than the 10th percentile), and placental abruption. A sample size of 232 women equally divided into two groups was needed to detect a significant reduction in primary outcome from 55% in the aspirin group to 36.7% in the enoxaparin-aspirin group (&agr;: 0.05, &bgr;: 0.8, two-sided). RESULTS: Between November 14, 2009, and February 21, 2015, 257 participants were enrolled. Baseline demographic and clinical factors were similar between groups. Eight women were excluded after randomization (six in the enoxaparin–aspirin group and two in the aspirin group), leaving 124 participants assigned to enoxaparin–aspirin and 125 to aspirin. Five participants were lost to follow-up (two in the enoxaparin–aspirin group and three in the aspirin group). There was no significant difference between the groups in the primary outcome: enoxaparin–aspirin 42 of 122 (34.4%) compared with aspirin alone 50 of 122 (41%) (relative risk 0.84, 95% confidence interval 0.61–1.16, P=.29). The occurrence of complications did not differ between the two groups. CONCLUSION: Antepartum prophylactic enoxaparin does not significantly reduce placenta-mediated complications in women receiving low-dose aspirin for previous severe preeclampsia diagnosed before 34 weeks of gestation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00986765.