Pessaries in multiple pregnancy as a prevention of preterm birth: the ProTwin Trial

Background

Preterm labour is the main cause of perinatal morbidity and mortality in the Western world. At present, there is evidence that tocolysis for 48 hours is useful in women with threatened preterm labour at least before 32 weeks. This allows transfer of the patient to a perinatal centre, and maximizes the effect of corticosteroids for improved neonatal survival. It is questionable whether treatment with tocolytics should be maintained after 48 hours.

Methods/Design

The APOSTEL II trial is a multicentre placebo-controlled study. Pregnant women admitted for threatened preterm labour who have been treated with 48 hours corticosteroids and tocolysis will be eligible to participate in the trial between 26⁺⁰ and 32⁺² weeks gestational age. They will be randomly allocated to nifedipine (intervention) or placebo (control) for twelve days or until delivery, whatever comes first. Primary outcome is a composite of perinatal death, and severe neonatal morbidity up to evaluation at 6 months after birth. Secondary outcomes are gestational age at delivery, number of days in neonatal intensive care and total days of the first 6 months out of hospital. In addition a cost-effectiveness analysis will be performed. Analysis will be by intention to treat. The power calculation is based on an expected 11% difference in adverse neonatal outcome. This implies that 406 women have to be randomised (two sided test, β 0.2 at alpha 0.05).

Discussion

This trial will provide evidence as to whether maintenance tocolysis reduces severe perinatal morbidity and mortality in women with threatened preterm labour before 32 weeks.

Trial Registration

Clinical trial registration: http://www.trialregister.nl, NTR 1336, date of registration: June 3^rd 2008.     

International consensus statement on the use of uterotonic agents during caesarean section

It is routine to give a uterotonic drug following delivery of the neonate during caesarean section. However, there is much heterogeneity in the relevant research, which has largely been performed in low-risk elective cases or women with uncomplicated labour. This is reflected in considerable variation in clinical practice. There are significant differences between dose requirements during elective and intrapartum caesarean section. Standard recommended doses are higher than required, with the potential for acute cardiovascular adverse effects. We recommend a small initial bolus dose of oxytocin, followed by a titrated infusion. The recommended doses of oxytocin may have to be increased in women with risk factors for uterine atony. Carbetocin at equipotent doses to oxytocin has similar actions, while avoiding the requirement for a continuous infusion after the initial dose and reducing the need for additional uterotonics. As with oxytocin, carbetocin dose requirements are higher for intrapartum caesarean sections. A second-line agent should be considered early if oxytocin/carbetocin fails to produce good uterine tone. Women with cardiac disease may be very sensitive to the adverse effects of oxytocin and other uterotonics, and their management needs to be individualised.     

Preeclampsia and genetic risk factors for thrombosis: a case-control study.

OBJECTIVE: Recently, it has been proposed that hereditary coagulation abnormalities leading to an increased venous thrombosis risk may play a role in the development of preeclampsia. We tested this hypothesis in women who have had preeclampsia compared with matched control subjects. STUDY DESIGN: We conducted a case-control study of 163 women with preeclampsia during 1991-1996. Control subjects were matched for age and delivery date. Patients and control subjects were tested for the presence of factor V Leiden, prothrombin 20210A allele, protein C, protein S, and antithrombin deficiency. Logistic regression methods were used for data analysis. RESULTS: The prevalence of these genetic risk factors was similar in the patient group (12.9%) and the control group (12.9%; odds ratio, 1.0; 95% confidence interval, 0.5-3.9). Unexpectedly, we found a high prevalence of factor V Leiden in the control group (9.2%). CONCLUSION: We found no differences in the prevalence of genetic risk factors of thrombosis in women with preeclampsia compared with control subjects.     

Psychometric evaluation of health-related quality of life measures in women after different types of delivery

OBJECTIVE: We examined the psychometric properties of three internationally established measures for health-related quality of life (HRQoL) in women after vaginal delivery (VD), elective cesarean section (CS), and emergency CS and the relationship of HRQoL scores with blood loss after delivery. METHODS: This is a prospective longitudinal study. One hundred forty-one consecutive patients (71 after VD, 36 after elective CS, and 34 after emergency CS) were enrolled in two university hospitals and one general hospital from June 2003 to March 2004. Women completed the Multidimensional Fatigue Inventory (MFI) and the EQ-5D classification of own health between 12 and 24 h after VD or between 24 and 48 h after CS. Subsequent assessments, additionally including the Short Form 36 (SF-36), were made 1, 3, and 6 weeks after delivery. We analyzed feasibility (response, completion time, reported difficulties, item nonresponse), reliability (Cronbach's alpha), discriminative validity between groups by type of delivery, and responsiveness over time (Wilcoxon's signed rank tests and effect sizes). RESULTS: The MFI, SF-36, and EQ-5D proved to be highly feasible and reliable (alpha>.7 for all scales of MFI and SF-36). The measures were able to discriminate between groups by mode of delivery and to detect moderate recovery in physical and small recovery in mental status over time in the first 6 weeks after delivery. The suboptimal total questionnaire response of 60% after 6 weeks was attributable to low response among women of non-Dutch ethnic origin. The significant correlation between Hb level and mean physical HRQoL scores found at T=0 disappeared 1 week postpartum. CONCLUSION: The combination of MFI, SF-36, and EQ-5D showed good psychometric performance and is a good choice to measure HRQoL after delivery in scientific studies. Development of a shorter set is needed for use in routine clinical practice.     

Conservative management of abnormally invasive placentation

Due to the growing number of cesarean deliveries, the frequency of abnormally invasive placentation is increasing. The optimal management of this condition remains unclear. This article reviews the efficacy and safety of conservative management of abnormally invasive placentation. We performed a MEDLINE and Embase search and reviewed all articles on conservative management of abnormally invasive placentation published from 1985 through 2006. Over the past 20 years, 48 reports have described outcomes of 60 women who were treated conservatively for abnormally invasive placentation. Twenty-six women were managed without any additional interventions. In most of these patients (19/26), the placenta had been partially removed. In 4 of these 26, conservative therapy failed. Twenty-two women received adjuvant methotrexate. In most of these women (19/22), the entire placenta was left in situ. In 5, therapy failed. Twelve women were managed with arterial embolization. In most of these (9/12), the diagnosis was made antepartum and the placenta was completely left in situ. In 3, therapy failed. Overall, 11 women experienced infection (11/60), 21 women experienced vaginal bleeding (21/60), and 4 suffered disseminated intravascular coagulopathy (4/60). Spontaneous loss of placental tissue was noted in 16 women. Subsequent pregnancies were reported in 8 women. Conservative management of abnormally invasive placentation can be effective and fertility can be preserved. It should only be considered in highly selected cases when blood loss is minimal and there is desire for fertility preservation. Whether adjuvant methotrexate or selective arterial embolization is beneficial is uncertain. Undetectable hCG values do not seem to guarantee complete resorption of retained placental tissue.     

Electroencephalography during normotensive and hypertensive pregnancy: a systematic review

The objective of this review was to evaluate the available medical literature concerning the electroencephalogram (EEG) during hypertensive disorders of pregnancy. All articles found during a MEDLINE and Embase database search on the subject of EEG differences associated with hypertensive disorders in pregnancy were screened for eligibility. In all, 22 articles which describe the EEG during preeclampsia (PE)/eclampsia were retrieved. Abnormal EEG findings were observed in the majority of the preeclamptic/eclamptic patients, consisting of slow waves most frequently localized in the occipital lobe, as well as spike discharges. The EEG abnormalities in PE/eclampsia were reversible in the majority of the cases. We conclude that these described abnormalities may be interpreted as a warning sign of deterioration of brain function in PE/eclampsia. However, some caution regarding this conclusion is advised because most of the retrieved articles were published in the 1950s and 1960s, and were not consistent with current clinical guidelines or medical terminology. Further research is needed to establish the clinical value of implementing EEGs in the assessment of the preeclamptic/eclamptic patient. TARGET AUDIENCE: Obstetricians & Gynecologists, Neurologists, Family Physicians. LEARNING OBJECTIVES: After completion of this educational activity, the obstetrician, gynecologist and neurologist should be better able to evaluate whether the EEG is normal for pregnancy; distinguish EEG abnormalities in hypertensive disorders in pregnancy, and assess the value of EEG abnormalities in preeclampsia (PE)/eclampsia for the detection of early signs of ischemia.