Bruno Langer

Plasma active renin, angiotensin I, and angiotensin II during pregnancy and in preeclampsia.

Objective To evaluate the activity of the renin-angiotensin-aldosterone system in the circulation during the three trimesters of normal pregnancy and in women with preeclampsia. Methods Normal pregnant volunteers (n = 7) were studied throughout pregnancy, and women with preeclampsia (n = 8) were studied in the third trimester. Plasma active renin and aldosterone were measured by radioimmunoassay. Angiotensin I and angiotensin II were determined by radioimmunoassay after separation of the peptides by high-performance liquid chromatography. Results Active renin concentration increased in the first trimester of normal pregnancy, whereas angiotensin I, angiotensin II, and aldosterone remained at a level comparable to the postpartum values. Highest activity of the renin-angiotensin-aldosterone system was observed during the third trimester with increased levels of angiotensin I, angiotensin II, and aldosterone. In contrast, in patients with preeclampsia, despite a slight increase of active renin levels, the other parameters of the renin-angiotensin-aldosterone system were low compared with the third trimester of normal pregnancy and were comparable to postpartum data. Conclusion Our results suggest that during the first trimester of normal pregnancy, active renin concentration in the plasma is increased and that renin is not the factor that limits angiotensin II synthesis. These results also confirm decreased activity of the renin-angiotensin-aldosterone system in preeclampsia. This could contribute to the diminished hemodynamic control observed in pregnant women developing preeclampsia.

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.

Prenatal sonographic diagnosis of skeletal dysplasias. A report of 47 cases.

The purpose of this study was to evaluate the foetal sonographic efficiency for prenatal diagnosis of osteochondrodysplasias. Forty-seven prenatal and postnatal cases diagnosed between January 1993 and December 1998 in the referral sonographic centres of Strasbourg were studied. All cases were reviewed retrospectively and the prenatal ultrasound findings and diagnosis were compared to the postnatal or post-mortem diagnosis. Each case was studied by ultrasonographers, geneticists, radiologists, and foetopathologists. Final diagnosis was based on clinical examination, skeletal survey and molecular testing as deemed necessary. Routine screening and dating was the indication for foetal sonography in 72% (32/47) of our cases. The most likely time of diagnosis was between 16 and 24 weeks of gestation (17 out of 47 cases, 36%), which corresponds to the time of foetal anomaly sonographic scan in France. The other cluster of cases (12 among 47, 26%) was disclosed before 16 weeks of gestation. These results illustrate the importance of a detailed evaluation of the limbs during sonographic examinations of first and second trimesters of pregnancy. While the identification of skeletal dysplasias was relatively easy in our study, the ability to make an accurate specific antenatal diagnosis was more difficult. An accurate diagnosis was proposed in 28 of the 47 cases (60%). In 19% of the cases (9/47), the prenatal diagnosis was not accurate; in 21% of the cases (10/47), the prenatal diagnosis was imprecise. In 45 of the 47 cases (96%) prenatal foetal scan correctly predicted the prognosis.

Multicenter study on the clinical value of fetal pulse oximetry

OBJECTIVE Our purpose was to compare the predictive value of intrapartum fetal pulse oximetry with that of fetal blood analysis for an abnormal neonatal outcome in case of an abnormal fetal heart rate. STUDY DESIGN A prospective multicenter observational study was conducted from June 1994 to November 1995. Fetal oxygen saturation was continuously recorded with a Nellcor N-400 fetal pulse oximeter in case of an abnormal fetal heart rate during labor. Simultaneous readings of fetal oxygen saturation and fetal blood analysis obtained before birth (i.e., either at full dilatation or before cesarean section when indicated) were compared with the neonatal status. The criteria for an abnormal neonatal outcome were (1) an umbilical arterial blood pH < or = 7.15 and (2) a combined variable including 5-minute Apgar score < or = 7, umbilical arterial pH < or = 7.15, secondary respiratory distress, transfer in a neonatal care unit, or neonatal death. RESULTS At a 7.20 threshold for fetal scalp pH and 30% for fetal oxygen saturation (i.e., the 10th percentile in the study population), the predictive value of fetal pulse oximetry was similar to that of fetal blood analysis for an arterial umbilical pH < or = 7.15 and for an abnormal neonatal outcome (positive predictive value 56% vs 55%, negative predictive value 81% vs 82%, sensitivity 29% vs 35%, and specificity 93% vs 91%, respectively). The receiver-operator characteristic curve showed similar performance of either technique for cutoff values < or = 7.20 for fetal blood pH and < or = 30% for fetal oxygen saturation, whereas fetal pulse oximetry became superior at higher thresholds. CONCLUSION The predictive value of intrapartum fetal pulse oximetry can be favorably compared with that of fetal blood analysis. Randomized controlled management trials can now be performed to assess potential clinical benefits of this new tool.

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.

Multicenter study on the clinical value of fetal pulse oximetry: I. Methodologic evaluation☆☆☆★

OBJECTIVE Our purpose was to evaluate the feasibility of intrapartum fetal pulse oximetry, the distribution of fetal oxygen saturation values, and the relationship with the neonatal outcome in a population with an abnormal fetal heart rate. STUDY DESIGN A prospective multicenter observational study was performed from June 1994 to November 1995. Fetal oxygen saturation was continuously recorded with use of a Nellcor N-400 fetal pulse oximeter in case of an abnormal fetal heart rate during labor. Simultaneous readings of fetal oxygen saturation and fetal blood analysis were obtained at inclusion and before birth. Feasibility, adverse effects, distribution of fetal oxygen saturation values, and relationship with neonatal outcome were assessed. RESULTS One hundred seventy-four patients were included. From 172 attempted sensor placements, the procedure was impossible in three cases and fetal oxygen saturation values were obtained in 164 cases (95.3%). Physicians considered sensor placement an easier task than an attempt at fetal blood analysis (easy in 87.5% vs 78.9% for fetal blood analysis, p = 0.03). The mean reliable signal time (+/- SD) was 64.7% +/- 32% during the first stage. There were no serious adverse effects in the study population. The mean fetal oxygen saturation during the first stage of labor was 42.2% +/- 8.0% (10th to 90th percentile range 30% to 53%). Fetal oxygen saturation was significantly correlated with scalp pH (r = 0.29, p = 0.01) but not with neonatal umbilical artery pH or gas values. There was a significant association between low fetal oxygen saturation (< 30%) and poor neonatal condition. CONCLUSION The feasibility of fetal pulse oximetry is satisfactory in clinical practice. It is easy to use and provides a fair rate of recorded values, even in a population with suspicion of fetal distress. A low fetal oxygen saturation is significantly associated with an abnormal neonatal outcome.

Postpartum hemorrhage: guidelines for clinical practice from the French ă College of Gynaecologists and Obstetricians (CNGOF) in collaboration ă with the French Society of Anesthesiology and Intensive Care (SFAR)

Postpartum haemorrhage (PPH) is defined as blood loss ≥500mL after delivery and severe PPH as blood loss ≥1000mL, regardless of the route of delivery (professional consensus). The preventive administration of uterotonic agents just after delivery is effective in reducing the incidence of PPH and its systematic use is recommended, regardless of the route of delivery (Grade A). Oxytocin is the first-line prophylactic drug, regardless of the route of delivery (Grade A); a slowly dose of 5 or 10 IU can be administered (Grade A) either IV or IM (professional consensus). After vaginal delivery, routine cord drainage (Grade B), controlled cord traction (Grade A), uterine massage (Grade A), and routine bladder voiding (professional consensus) are not systematically recommended for PPH prevention. After caesarean delivery, placental delivery by controlled cord traction is recommended (grade B). The routine use of a collector bag to assess postpartum blood loss at vaginal delivery is not systematically recommended (Grade B), since the incidence of severe PPH is not affected by this intervention. In cases of overt PPH after vaginal delivery, placement of a blood collection bag is recommended (professional consensus). The initial treatment of PPH consists in a manual uterine examination, together with antibiotic prophylaxis, careful visual assessment of the lower genital tract, a uterine massage, and the administration of 5-10 IU oxytocin injected slowly IV or IM, followed by a maintenance infusion not to exceed a cumulative dose of 40IU (professional consensus). If oxytocin fails to control the bleeding, the administration of sulprostone is recommended within 30minutes of the PPH diagnosis (Grade C). Intrauterine balloon tamponade can be performed if sulprostone fails and before recourse to either surgery or interventional radiology (professional consensus). Fluid resuscitation is recommended for PPH persistent after first line uterotonics, or if clinical signs of severity (Grade B). The objective of RBC transfusion is to maintain a haemoglobin concentration (Hb) >8g/dL. During active haemorrhaging, it is desirable to maintain a fibrinogen level ≥2g/L (professional consensus). RBC, fibrinogen and fresh frozen plasma (FFP) may be administered without awaiting laboratory results (professional consensus). Tranexamic acid may be used at a dose of 1 g, renewable once if ineffective the first time in the treatment of PPH when bleeding persists after sulprostone administration (professional consensus), even though its clinical value has not yet been demonstrated in obstetric settings. It is recommended to prevent and treat hypothermia in women with PPH by warming infusion solutions and blood products and by active skin warming (Grade C). Oxygen administration is recommended in women with severe PPH (professional consensus). If PPH is not controlled by pharmacological treatments and possibly intra-uterine balloon, invasive treatments by arterial embolization or surgery are recommended (Grade C). No technique for conservative surgery is favoured over any other (professional consensus). Hospital-to-hospital transfer of a woman with a PPH for embolization is possible once hemoperitoneum is ruled out and if the patients hemodynamic condition so allows (professional consensus).

Incidence and distribution of pathogens in early-onset neonatal sepsis in the era of antenatal antibiotics.

In 2001 France issued a new set of guidelines for the use of antenatal antibiotics (AA). These guidelines recommended intrapartum antimicrobial prophylaxis (IAP) to prevent group B streptococcal (GBS) disease and AA to prolong pregnancy in the event of preterm premature rupture of membranes (AA for PPROM). This study aims to determine the effects of AA, recommended by national guidelines, on the incidence and distribution of pathogens in early-onset neonatal sepsis (EONS). We performed a population-based, prospective, observational study of level II and III perinatal centres throughout the region of Alsace, a northeastern area of France, between March 2004 and February 2005. The study population included all neonates with confirmed or probable EONS, who were treated with antibiotics for at least 5 days. We analysed exposure to AA, as well as clinical and microbiological data obtained from medical records. A total of 20 131 neonates were born during the study period, and 217 were included in the study. Of these, 24 subjects had confirmed sepsis, 140 had probable sepsis and 53 had possible EONS. The overall incidence of confirmed EONS was 1.19 per 1000 births. The infecting bacteria was GBS in 15 of 24 (62.5%) confirmed EONS cases (incidence: 0.75 per 1000 births) and in 81 of 140 (58%) probable sepsis cases. Escherichia coli was identified in 6 of 24 (25%) cases of confirmed EONS (incidence: 0.3 per 1000 births) and in 30 of 140 (21%) cases of clinical sepsis. Among E. coli infections (n= 36), amoxicillin resistance (n= 18) was statistically linked with AA use (P = 0.045). This link was significant in cases of PPROM (P = 0.015), but not when IAP was administered to prevent GBS disease (P = 0.264). IAP was not performed in 18 of 60 (30%) cases and 32 of 93 (34%) cases, despite positive screening or the presence of risk factors for EONS, respectively. Group B streptococcus remains the predominant pathogen in the era of AA. Aminopenicillin-resistant E. coli infections seem to be linked to prolonged AA in cases of PPROM and appear to preferentially affect preterm infants. Therefore, postnatal treatment strategies should consider this possible effect. Our data indicate that the current policy of GBS maternal prophylaxis is not associated with an excessive risk of pathogen resistance. Considering the high incidence of GBS EONS in our region, possible progress could result from better observance of guidelines. These results strengthen the need for continuation of surveillance.

Late-onset neonatal infections: incidences and pathogens in the era of antenatal antibiotics

Widespread use of intrapartum antimicrobial prophylaxis has significantly reduced the incidence of early-onset neonatal infection (EONI); however, little is known about the effects of increased maternal exposure to antibiotics on late-onset neonatal infection (LONI). This study aims to evaluate LONI epidemiology in our region after the application of French recommendations and to determine whether LONI-causing organisms and their antibiotic susceptibility are influenced by peripartum antibiotic exposure. We performed a prospective epidemiologic study of 139 confirmed and possible cases of bacterial LONI in patients treated with antibiotics for at least 5 days of the 22,458 infants born in our region in the year 2007. The overall incidence of LONI caused by all pathogens, Group B streptococcus (GBS) and Escherichia coli (E. coli) were 6.19, 0.36 and 2.72, respectively, per 1,000 live births. Our findings revealed three major types of LONI: E. coli-induced urinary tract infection (UTI) among term infants, coagulase negative Staphylococcus septicemia affecting preterm infants, and GBS infections with severe clinical presentation. Univariable analysis revealed that maternal antibiotic exposure was significantly associated with the risk of amoxicillin-resistant E. coli infection (p = 0.01). Postnatal antibiotic exposure was associated with an increased risk of E. coli LONI (p = 0.048). This link persisted upon multivariable analysis; however, no additional risk factors were identified for LONI caused by antibiotic-resistant E. coli. Conclusion Our findings confirm that despite the benefits of antenatal antibiotics, this treatment can increase the risk of antibiotic-resistant cases of LONI. National and international surveillance of LONI epidemiology is essential to assess benefits and potential negative consequences of perinatal antibiotic exposure.

Antenatal Diagnosis of Brain Damage in the Survivor after the Second Trimester Death of a Monochorionic Monoamniotic Co-Twin

At 28 weeks of amenorrhea, 1 fetus of a monoamniotic twin pregnancy died. Ultrasound and Doppler investigations of the surviving twin were normal. Three weeks later, endovaginal ultrasound and magnetic resonance imaging revealed massive bilateral cerebral ischemic necrosis in the surviving twin. In utero fetal blood sampling carried out before the termination did not reveal either anemia or thrombopenia. Current data suggest that cerebral or renal ischemic complications could set in immediately after the death of the first twin as a result of a period of acute hypotension. At least 2 weeks are necessary for them to be identifiable by ultrasound. It seems that they cannot be prevented by prompt delivery of the second twin.