Philippe Deruelle

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).

Delivery for women with a previous cesarean: guidelines for clinical practice from the French College of Gynecologists and Obstetricians (CNGOF).

The primary cause of uterine scars is a previous cesarean. In women with a previous cesarean, the risks of maternal complications are rare and similar after a trial of labor after cesarean (TOLAC) and after an elective repeat cesarean delivery (ERCD), but the risk of uterine rupture is higher with TOLAC (level of evidence [LE]2). Maternal morbidity in women with previous cesareans is higher when TOLAC fails than when it leads to successful vaginal delivery (LE2). Although maternal morbidity increases progressively with the number of ERCD, maternal morbidity of TOLAC decreases with the number of successful previous TOLAC (LE2). The risk-benefit ratio considering the risks of short- and long-term maternal complications is favorable to TOLAC in most cases (LE3). Globally, neonatal complications are rare regardless of the mode of delivery for women with previous cesareans. The risks of fetal, perinatal, and neonatal mortality during TOLAC are low. Nonetheless, these risks are significantly higher than those associated with ERCD (LE2). The risks of mask ventilation, intubation for meconium-stained amniotic fluid, and neonatal sepsis all increase in TOLAC (LE2). The risk of transient respiratory distress increases in ERCD (LE2). To reduce this risk, and except in particular situations, ERCD must not be performed before 39 weeks (grade B). TOLAC is possible for women with a previous cesarean before 37 weeks, with 2 previous cesareans, with a uterine malformation, a low vertical incision or an unknown incision, with a myomectomy, postpartum fever, an interval of less than 6 months between the last cesarean delivery and the conception of the following pregnancy, if the obstetric conditions are favorable (professional consensus). ERCD is recommended in women with a scar in the uterine body (grade B) and a history of 3 or more cesareans (professional consensus). Ultrasound assessment of the risk of uterine rupture in women with uterine scars has not been shown to have any clinical utility and is therefore not recommended during pregnancy to help decide the mode of delivery (professional consensus). Use of X-ray pelvimetry to decide about TOLAC is associated with an increase in the repeat cesarean rate without any reduction in the rate of uterine rupture (LE2). It is unnecessary for deciding mode of delivery and for managing labor during TOLAC (grade C). TOLAC should be encouraged for women with a previous vaginal delivery either before or after the cesarean, a favorable Bishop score or spontaneous labor, and for preterm births (grade C). For women with a fetus with an estimated weight of more than 4500 g, especially in the absence of a previous vaginal delivery and those with supermorbid obesity (BMI>50), ERCD must be planned from the outset (grade C). For all of the other clinical situations envisioned (maternal age>35 years, diabetes, morbid obesity, prolonged pregnancy, breech presentation and twin pregnancy), TOLAC is possible but the available data do not allow specific guidelines about the choice of mode of delivery, in view of the low levels of proof (grade C). The decision about planned mode of delivery must be shared by the patient and her physician and made by the 8th month, taking into account the individual risk factors for TOLAC failure and uterine rupture (professional consensus). TOLAC is the preferred choice for women who do not have several risk factors (professional consensus). The availability onsite of an obstetrician and anesthetist must be pointed out to the patient. If the woman continues to prefer a repeat cesarean after adequate information and time to think about it, her preference should be honored (professional consensus). Labor should be induced in woman with a previous cesarean only for medical indications (professional consensus). Induction of labor increases the risk of uterine rupture, which can be estimated at 1% if oxytocin is used and 2% with vaginal prostaglandins (LE2). Mechanical methods of induction have not been studied sufficiently. Misoprostol appears to increase the risk of uterine rupture strongly (LE4). Based on the information now available, its use is not recommended (professional consensus). Routine use of internal tocodynamometry does not prevent uterine rupture (professional consensus). The increased risk of uterine rupture associated with oxytocin use is dose-dependent (LE3). In the active phase, it is recommended that the total duration of failure to progress should not exceed 3h; at that point, a cesarean should be performed (professional consensus). Epidural analgesia must be encouraged. The simple existence of a uterine scar is not an indication for a routine manual uterine examination after VBAC (grade 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.

Long-term prognosis for infants after massive fetomaternal hemorrhage.

OBJECTIVE: To evaluate the fetal, neonatal, and long-term prognosis of massive fetomaternal hemorrhage (20 mL or more). METHODS: This series includes all patients with Kleihauer test values of 40 per 10,000 or higher over an 8-year period at two university hospitals. We examined obstetric, neonatal, and subsequent outcome data for the children. RESULTS: During the study period, 48 patients had massive fetomaternal hemorrhage (crude incidence 1.1 per 1,000; corrected incidence for Rh-negative women 4.6 per 1,000). Six fetal deaths were observed, representing 1.6% of all fetal deaths during the period. Nine newborns (18.7%) were transferred to neonatal intensive care unit (NICU) and five (10.4%) had transfusions. Fetomaternal hemorrhages of 20 mL/kg or more significantly increased the risk of fetal death, induced preterm delivery, transfer to NICU, and neonatal anemia requiring transfusion. Long-term follow-up was not associated with neurological sequelae (0%, 95% confidence interval 0.0–11.6%). CONCLUSION: When the transfused volume equals or exceeds 20 mL/kg, massive fetomaternal hemorrhage may lead to severe prenatal or neonatal complications. LEVEL OF EVIDENCE: III

Time course analysis of RNA stability in human placenta

BackgroundEvaluation of RNA quality is essential for gene expression analysis, as the presence of degraded samples may influence the interpretation of expression levels. Particularly, qRT-PCR data can be affected by RNA integrity and stability. To explore systematically how RNA quality affects qRT-PCR assay performance, a set of human placenta RNA samples was generated by two protocols handlings of fresh tissue over a progressive time course of 4 days. Protocol A consists of a direct transfer of tissue into RNA-stabilizing solution (RNAlater™) solution. Protocol B uses a dissection of placenta villosities before bio banking. We tested and compared RNA yields, total RNA integrity, mRNA integrity and stability in these two protocols according to the duration of storage.ResultsA long time tissue storage had little effect on the total RNA and mRNA integrity but induced changes in the transcript levels of stress-responsive genes as TNF-alpha or COX2 after 48 h. The loss of the RNA integrity was higher in the placental tissues that underwent a dissection before RNA processing by comparison with those transferred directly into RNA later™ solution. That loss is moderate, with average RIN (RNA Integration Numbers) range values of 4.5–6.05, in comparison with values of 6.44–7.22 in samples directly transferred to RNAlater™ (protocol A). Among the house keeping genes tested, the B2M is the most stable.ConclusionThis study shows that placental samples can be stored at + 4°C up to 48 h before RNA extraction without altering RNA quality. Rapid tissue handling without dissection and using RNA-stabilizing solution (RNAlater™) is a prerequisite to obtain suitable RNA integrity and stability.

Management of interstitial pregnancy using selective uterine artery embolization

BACKGROUND: Interstitial pregnancy is a rare and dangerous form of ectopic pregnancy which is treated by surgery, medical treatment, or both. Management options are not standardized. Currently, conservative nonsurgical treatment seems to be an alternative method in case of interstitial pregnancy. CASE: A right interstitial pregnancy was diagnosed in a 28-year-old woman. She was successfully treated by 2 courses of systemic methotrexate (1mg/kg) 24 hours apart followed by selective uterine artery embolization. The postembolization course was uneventful, and no rupture occurred. Ten weeks after embolization, human chorionic gonadotropin level was negative. CONCLUSION: Uterine embolization associated with methotrexate can be used successfully in treating selected cases of early interstitial pregnancy. We hypothesize that this procedure combined with methotrexate could reduce hemorrhagic risk.

Role of the alpha2-adrenoceptors on the pulmonary circulation in the ovine fetus

Recent in vitro studies reported that nitric oxide release and pulmonary vasorelaxation can be mediated by endothelial α2-adrenoceptor activation. As norepinephrine (α1-,α2-, and β1-adrenoceptor agonist) was found to induce pulmonary vasodilation in the ovine fetus, we hypothesized that α2-adrenoceptors may modulate basal pulmonary vascular tone and mediate the vascular effect of norepinephrine during fetal life. To determine the role of α2-adrenoceptors and the mechanisms of norepinephrine-mediated vasodilation in the fetal pulmonary circulation, we tested, in chronically prepared late-gestation fetal lambs, the hemodynamic response to 1) yohimbine (α2 antagonist); 2) UK 14,304 (α2 agonist) with and without L-nitro-arginine (nitric oxide synthase inhibitor); and 3) norepinephrine infusion with and without yohimbine. We found that yohimbine increased mean pulmonary artery pressure by 15% (p < 0.05), decreased pulmonary flow by 22% (p < 0.01), and increased pulmonary vascular resistance by 51% (p < 0.01). UK 14,304 increased pulmonary flow by 145% (p < 0.01) and decreased pulmonary vascular resistance by 58% (p < 0.01). L-Nitro-arginine abolished the UK 14,304-mediated pulmonary vasodilation. Norepinephrine (0.5 μg·kg−1·min−1) increased both pulmonary flow by 61% (p < 0.01) and pulmonary arterial pressure by 13% (p < 0.01) and decreased pulmonary vascular resistance by 33% (p < 0.01). Yohimbine abolished the norepinephrine-induced pulmonary vasodilation. This study suggests that 1) a basal α2-adrenoceptor activation-induced pulmonary vasodilation exists during fetal life; 2) the pulmonary vascular effects of α2-adrenoceptor activation are related at least in part to nitric oxide production; and 3) the norepinephrine-mediated pulmonary vasodilation involves α2-adrenoceptor activation. As a surge of norepinephrine exists at birth, we speculate that norepinephrine and endothelial α2-adrenoceptor activation may play a significant role in pulmonary vasodilation at birth.

Successful in utero treatment of chronic and massive fetomaternal hemorrhage with fetal hydrops.

Background: Massive fetomaternal hemorrhage is an uncommon cause of chronic fetal anemia. Without treatment, hydrops fetalis can occur and progress toward death. In some cases, an early diagnosis can improve the management. Case: A patient was found to have a fetus with non-immune hydrops related to massive and early fetomaternal hemorrhage successfully treated with serial fetal intravascular transfusion. After the treatment, ultrasonographic signs of hydrops disappeared and the pregnancy resulted in a good fetal outcome. There was no need for neonatal transfusion. Neurological examination at 1 month post-natal was normal. Conclusion: When massive fetomaternal hemorrhage is diagnosed early in the pregnancy, serial fetal intravascular transfusion may be an alternative to immediate delivery.

A case–control study of placental lesions associated with pre-eclampsia

To investigate gross and microscopic placental lesions associated with pre‐eclampsia and to determine which lesions are most strongly linked to serious pregnancy complications.

Effects of n-3 polyunsaturated fatty acids in the fetal pulmonary circulation.

Objective: Although evidence exists that n-3 polyunsaturated fatty acids may improve the outcome in patients with severe respiratory failure, little is known regarding their pulmonary circulatory effects. This question is clinically relevant in respiratory failure associated with pulmonary hypertension, in particular in newborn infants with persistent pulmonary hypertension. The objective of this study was to investigate the effects of n-3 polyunsaturated fatty acids on the fetal pulmonary circulation. Design: Randomized, placebo-controlled comparative laboratory investigation. Setting: University research facility. Subjects: Fifty-two chronically prepared lamb fetuses. Interventions: Catheters and ultrasonic flow transducer were placed through a left thoracotomy in the lamb fetus to determine aortic, pulmonary, and left atrial pressures and left pulmonary artery blood flow. Measurements and Main Results: We compared the pulmonary vascular responses to 120 mins of Omegaven (lipid emulsions enriched in n-3 polyunsaturated fatty acids) or Intralipide (lipid emulsions enriched in n-6 polyunsaturated fatty acids) infusion. Then we investigated the effects of Omegaven on the pulmonary circulation after nitric oxide synthase inhibition by l-nitro-arginine, potassium channel blockade by tetraethylammonium, and cytochrome P450 epoxygenase inhibition by (methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Pulmonary artery and aortic pressures as well as blood gases and plasma lactate concentrations did not change during either fat emulsion infusion. Left pulmonary blood flow increased by 30% and pulmonary vascular resistance decreased by 28% during Omegaven infusion, whereas left pulmonary blood flow and pulmonary vascular resistance did not change during Intralipide infusion. This pulmonary vascular response to Omegaven was not altered by l-nitro-arginine. At the opposite, Omegaven induced pulmonary vasodilatation was abolished by tetraethylammonium and markedly attenuated by (methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Conclusions: Lipid emulsion containing n-3 polyunsaturated fatty acids may induce a potent and sustained vasodilatation in the fetal lung. This pulmonary vasodilator response is mediated through production of vasoactive mediators by cytochrome P450 epoxygenase and through activation of potassium channels.