Retained Placenta

The incidence and importance of retained placenta (RP) varies greatly around the world. In less developed countries, it affects about 0.1% of deliveries but has up to 10% case fatality rate. In more developed countries, it is more common (about 3% of vaginal deliveries) but very rarely associated with mortality. There are three main types of retained placenta following the vagina delivery: placenta adherens (when there is failed contraction of the myometrium behind the placenta), trapped placenta (a detached placenta trapped behind a closed cervix) and partial accreta (when there is a small area of accreta preventing detachment). All can be treated by manual removal of placenta, which should be carried out at 30–60 minutes postpartum. Medical management is also an option for placenta adherens and trapped placenta. The need for manual removal can be reduced by 20% by the use of intraumbilical oxytocin (30 i.u. in 30 mL saline). A trapped placenta may respond to glyceryl trinitrate (500 mcg sublingually) or gentle, persistent, controlled cord traction. Key words oxytocin postpartum haemorrhage retained placenta third stage of labour Introduction The incidence of retained placenta (RP) varies greatly around the world, affecting between 0.1 and 3.3% of vaginal deliveries depending on the population studied (see Table 1 ). Fortunately, however, there is also a regional variation in the risk associated with it, with the case fatality rate being inversely proportional to the incidence. Where there is easy access to hospital care and transfusion, mortality from this condition is very low. In the UK, the death rate from RP has shown repeated falls since the collection of maternal mortality data began in 1925. Between 1925 and 1930 there were 301 recorded deaths from retained and adherent placenta, a ratio of 7.5 per 100,000 live births. 1 This figure is similar to the total maternal mortality rate in the UK today. By contrast, between 1969 and 2005 in the UK there was only one death from postpartum haemorrhage (PPH) caused by an RP, although some extra deaths were recorded from placental inversion, placenta accreta and complications of treatment. The 1996–9 triennial report described a death from PPH secondary to RP for the first time in 30 years. 2 From the Confidential Enquiries into Maternal Deaths (CEMD) data, the estimated death rate from RP in the UK is 1 in every 20 million deliveries, or an estimated 1 death for every 400,000 RPs. In many parts of the developing world, however, the case fatality rate from RP is high. In an observational study from rural India, in which traditional birth attendants delivered the majority of women at home, there were two deaths (9%) from among the 22 women who had placental retention of over 60 minutes. 3 In a large northern Nigerian hospital, the mortality was 3% amongst 894 women treated for RP over a 3½-year period. 4 The cause of death is usually haemorrhage. This is more frequent when facilities for manual removal of placenta (MROP) are not immediately available or when travelling times to hospital are long. Clearly, an effective medical treatment could have major implications for the reduction of maternal mortality. 5 Definition and terminology There is no consensus as to the length of the third stage after which a placenta should be called ‘retained’. In Europe, manual removals of placentas are advised at anything between 20 minutes and over 1 hour into the third stage. 6 The choice of timing is a balance between the PPH risk of leaving the placenta in situ , the likelihood of spontaneous delivery and the knowledge from caesarean study (CS) studies that the manual removal itself causes haemorrhage. 7 In a study of over 12,000 births, Combs and Laros found that the risk of haemorrhage increased after 30 minutes. 8 Similarly, Magann et al found that the risk of haemorrhage increased with time. In their study, the risk of PPH was already significantly increased at 10 minutes and, using a receiving operator characteristic (ROC) curve, they demonstrated that the optimal cut-off time for the prediction of PPH was 18 minutes. 9 However, delaying the manual removal will lead to the spontaneous delivery of many placentas. In the control arms of trials of umbilical oxytocin for the treatment of RP, 42% of placentas delivered spontaneously without any intervention in the 30 minutes following recruitment (which was mainly between 15 and 30 minutes after delivery). 10 By contrast, in the only randomised trial to recruit after 60 minutes of the third stage had elapsed, the spontaneous delivery rate over the subsequent 30 minutes in the control group was 0%. 11 Clearly, the choice of timing for manual removal depends on the facilities available and the local risks associated with both PPH and MROP. Thus the 2007 intrapartum guidelines produced for the UK government agency NICE (National Institute for Health and Clinical Excellence) suggest 30 minutes 12 , whereas the WHO manual for childbirth suggests 60 minutes. 13 Almost all studies into the ‘normal’ duration of the third stage have been conducted in the context of the active management of the third stage of labour, using prophylactic oxytocics. But these have a marked effect on the length of the third stage, so that it is inaccurate to call it ‘normal’, even if active management is generally accepted to be the standard of care. In the active vs. physiological management Cochrane review, the mean length of the third stage in those who had physiological management was 15.5 minutes, compared with 8.8 minutes in those who had active management. 14 This translates into a reduction in the number of placentas still in situ at 20 and 40 minutes ( Figure 1 ). When the numbers who actually need manual removal are compared, however, there is no difference between the two groups. Taking this into account in the definition of a prolonged third stage, the NICE intrapartum guidelines define a prolonged third stage following physiological management as 60 minutes. 12 It has long been recognised that the term ‘retained placenta’ covers a number of pathologies. Some placentas are simply trapped behind a closed cervix (the ‘incarcerated’ or ‘trapped placenta’), some are adherent to the uterine wall but easily separated manually (‘placenta adherens’) whereas others are pathologically invading the myometrium (placenta accreta). A prospective analysis of deliveries in Liverpool Women's Hospital from 2005 to 2006 found that there were 287 third stages of over 30 minutes (a rate of 3.3%). Of the 127 that required manual removal, 81% were ‘placenta adherens’ type, 6% had some areas of accreta (i.e. the placenta had to be removed piecemeal) and 13% were ‘trapped’ (Khan, unpublished data). None required hysterectomy for placenta accreta. This is in contrast to the data from Rogers et al, who found that of manual removals following recruitment to a PPH prophylaxis trial in Hinchingbrooke, 51% were described by the operator as being trapped. 15 Placenta accreta is thought to have an incidence of 1:2510,16 although this does not include the many placentas in which a clear plane of separation cannot be identified at MROP and in whom the placenta is removed piecemeal. It is likely that in most of these there is a small area of accreta. The close association of placenta accreta with both previous caesarean section (CS) and placenta praevia means that it rarely presents as an RP after vaginal delivery. In the series of 62 cases by Millar, all but seven were associated with placenta praevia and they were all delivered by CS. 16 In the absence of placenta praevia, therefore, the placenta accreta rate was 1 in 22,000. Assuming an RP rate of 2%, this suggests that around 1 in 440 women with an RP following vaginal delivery will have placenta accreta. More details on the antenatal diagnosis and management of placenta accreta are found in the review by Palcaios Jaraquemada. 17 Epidemiology There is a considerable variation in the retained placenta rate between countries. Table 1 presents an analysis of geographical variation in RP rates in which ten observational studies of over 3000 participants were compared. The studies used injectable oxytocics and a definition of 30–40 minutes for a retained placenta. The combined RP rate in those countries classified as ‘least developed’ by the UN was 0.17% compared to a rate of 2.5% for those classified as ‘most developed’ [ Table 1 ; relative risk (RR) 14.0, 95% confidence interval (CI) 11.2–17.5]. Reasons for this difference in prevalence between the least and most developed countries, as well as the observed increase in RP rates with increasing development 18 , relate to the differences in aetiological factors for a prolonged third stage. These were studied in a series of 13,000 deliveries by Combs and Laros.8 Logistical regression identified nine factors that were independently associated with a third stage of over 30 minutes. The strongest association was with gestational age ( Figure 2 ), but high rates of RP were also found with delivery in a labour bed (rather than standing or squatting), pre-eclampsia and previous abortions, extremes of parity or age, use of oxytocin, non-Asian race and midwifery deliveries. Similarly, in a case-control study from Saudi Arabia, 114 women with RP were compared to 116 with normal third stages. 19 Logistical regression analysis showed significant associations of RP with multiparity, induced labour, small placenta, high blood loss, high pregnancy number, previous uterine injury and pre-term labour. These studies suggest that interventions common in the most developed countries (abortions, labour induction, use of oxytocin) might be contributing to their high RP rates. Overall, there are no differences in RP rates between those who undergo physiological and active management of the third stage of labour. 14 However, there are major differences between the results of individual trials within the meta-analysis. This occurs primarily as a result of the Dublin trial. 20 This was the only trial to study intravenous ergometrine, and it shows a massive increase in the need for MROP with the oxytocic (RR 19.5, 95% CI 2.6–145.4). This is likely to be a peculiarity of ergometrine, which, unlike oxytocin, causes a powerful, continuous uterine contraction. With intravenous administration its onset is immediate and this closes the cervix at the same time as the placental detachment occurs, thus trapping the placenta behind a closed cervix. The association of RP with the use of ergometrine was supported by data from a population study in Sweden. 21 The RP rate in ten centres that routinely used methylergometrine 0.2 mg was 2.7%, compared to 1.8% in those that used oxytocin 5 or 10 units alone ( P < 0.001). It has also been suggested that uterine abnormalities might be an aetiological factor for RP. Indeed, in a series of 63 pregnancies in women with Mullerian duct fusion abnormalities, 11 (17%) had RP. 22 However, given the rarity of these abnormalities in the general population (0.2%), it would not seem necessary to investigate every woman with an RP for uterine abnormalities. Indeed, in the Green and Harris series 22 , the chance of any one woman with an RP having a Mullarian duct abnormality would only have been 1.5%, assuming an RP rate of 2%. Subtle abnormalities might, however, be more common. Golan et al conducted routine hysteroscopy 6 weeks after MROP in 48 women 23 ; they found an incomplete uterine septum in 15%. Following an RP in any previous pregnancy, there is an overall recurrence rate of 6.25%. 18 The risk of RP in the second pregnancy rises from 2% to 4.8% if there was an RP in the first. From our understanding of the aetiology and pathophysiology of RP, a theoretical model of RP can be built up to include pathophysiology, aetiology and treatment ( Table 2 ). Studies of treatment have not previously included pathophysiology into their inclusion and exclusion criteria. It is not possible, therefore, to test this hypothesis from previous studies. However, it could partially explain why the RP rate varies greatly throughout the world, and why both oxytocics and uterine relaxants have been found to have high success rates. Pathophysiology of placenta adherens Ultrasound studies Ultrasound studies of the third stage of labour have improved the understanding of both the normal and abnormal third stage of labour. Herman et al first demonstrated ultrasonographically that a retroplacental myometrial contraction is mandatory to produce shearing forces on the interface between the placenta and myometrium, and to lead to its detachment. 24 He divided the third stage into four phases according to the ultrasound appearances. In the latent phase, which immediately follows delivery of the fetus, all the myometrium contracts, except for that behind the placenta, which remains relaxed. In the contraction phase, the retroplacental myometrium contracts, leading to the detachment phase, when the placenta is sheared away from the decidua. In the expulsion phase, the placenta is expelled from the uterus by uterine contraction. Contractions occurring prior to delivery are insufficient to cause placental detachment as in the presence of the fetus, the myometrium is unable to achieve the necessary strain for detachment. 25 These ultrasound studies also shed light on the aetiology of the RP. They demonstrate that the duration of the third stage of labour is dependent on the length of the latent phase and that a prolonged third stage is due to contractile failure in the retroplacental area. 24 In the cases of RP in which Herman et al conducted serial ultrasonographic myometrial thickness measurements, they found a universal failure of retroplacental contraction. 24 The finding that women with placenta adherans have retroplacental contractile failure might explain the fact that RP and dysfunctional labour have been shown to be closely associated 8 , even though all women with severe dysfunctional labour are delivered by CS. Indeed, observational studies have shown that women undergoing CS for dysfunctional labour have to have their placenta removed manually after CS more often than those undergoing elective CS. 26 Furthermore, on ultrasound there appear to be fewer retroplacental contractions in dysfunctional labours than in normally progressing labours. 27 Both studies suggest that there is a localised failure of myometrial contractility in some women, resulting in dysfunctional labour and retained placenta. If the failure is complete, then a CS results. If it is partial, then the woman might achieve vaginal delivery but have a retained placenta. The relative lack of contractile strength in the retroplacental myometrium might make evolutionary sense for both the mother and fetus. During strong contractions it not only prevents inadvertent placental detachment, but also allows good blood flow to the placenta to be maintained. These studies suggest that the problem of RP might be solved by stimulating contractions in the retroplacental myometrium. This could be achieved by providing local stimulation with oxytocics, delivered to the placenta via the umbilical vein. Management Prophylaxis There is little data on the use of techniques for the prevention of retained placentas. As can be seen above, although the use of prophylactic oxytocics reduced the mean length of the third stage, they have no effect on need for manual removal. Care of the cord (early clamping or drainage of cord blood) has also been examined to see if there is an effect on retained placenta rates. 28 Only one study has examined the effect of cord drainage on RP rates and this showed a marked decrease in the number of retained placentas in those who underwent cord drainage (RR 0.28, 95% CI 0.10--0.73). It is not know whether this is also true for delayed cord clamping, as this has not been tested in any published study. Likewise, the effect of cord traction has never been studied in a randomised trial independent of the other components of the active management of the third stage. 29 Some authors have examined the potential of giving every woman a prophylactic intraumbilical oxytocin injection as a way of conducting an active management of the third stage of labour without the need for systemic drugs. 30 However, to estimate the effect of this on the incidence of this on PPH or RP would take studies of many thousands and the largest study to date only has 200 participants. 31 There is therefore currently insufficient evidence to suggest this procedure. Diagnosis of the type of retained placenta In a normal clinical setting, the differentiation between a placenta that is ‘trapped’ and adherent (placenta adherens) is not easy unless ultrasound is used. Placenta accreta is rare in women having a vaginal delivery, and will usually be discovered only at the time of attempted manual removal. Clues to a trapped placenta will be if the fundus feels small and contracted, or if the edge of the placenta is palpable through a tight cervical os. By contrast, the fundus is usually soft and wide with a placenta adherens. Herman et al suggest that ultrasound should be used to differentiate between a trapped and an adherent placenta. 24 With a trapped placenta, the myometrium is seen to be thickened all around the uterus and a clear demarcation is often seen between the placenta and the myometrium. By contrast, with an adherent placenta, the myometrium will be thickened in all areas except where the placenta is attached where it will be very thin or even invisible ( Figure 3 ). Treatment options Systemic oxytocics The finding that prophylactic oxytocin injections (which last in the circulation for only 10 min) increase the number of placentas delivered in the first 30 minutes after delivery, provides the theoretical basis for the use of oxytocics to try and deliver the remainder. Although the use of an IV infusion of oxytocin for the treatment of RP has never been subjected to a randomised trial, a large cluster trial has demonstrated that early postnatal nipple stimulation has no effect. 32 Similarly, sustained uterine stimulation with misoprostol given immediately postpartum (which lasts in the circulation for around 2 hours when given orally) does not affect the rate of RP compared to short-acting IV/IM oxytocin. 33 From this it seems unlikely that it would have any beneficial effect if given to a woman with an RP. However, there is some evidence that an intravenous infusion of sulprostone, a synthetic-E2 prostaglandin, might be beneficial. In a placebo-controlled, double-blind randomised trial, van Beekhuizen et al found that sulprostone successfully delivered the placenta in 52% of RPs, compared with 18% for placebo ( P = 0.03). 34 Umbilical vein oxytocin injection The notion that oxytocin can be delivered directly to the retroplacental myometrium by injecting it into the placental bed via the umbilical vein has stimulated a lot of interest. This technique allows the oxytocic to be directed specifically at the area with the contractile failure, sparing the remainder. Results from trials of this treatment have been mixed. A Cochrane review concludes that the use of umbilical oxytocin is effective in the management of RP, despite the fact that the meta-analysis showed the reduction in RP rates not to be significantly different to that obtained with expectant management (RR 0.86, 95% CI 0.72–1.01). 10 The basis for this conclusion was data from trials in which umbilical oxytocin was compared to placebo, which showed a significant reduction in need for MROP with umbilical oxytocin injection (RR 0.79, 95% CI 0.69–0.91). On this basis, the recent NICE guidelines in the UK have recommended the use of umbilical oxytocin for the treatment of RP. 12 The inconclusive results from randomised trials might be due to inadequate delivery of the oxytocin to the retroplacental myometrium. Pipingas et al found that the method of injection used in most trials resulted in capillary filling in only 20–60% of cases. 35 They found that the best results from in-vitro studies were achieved with oxytocin diluted in 30 mL saline and injected down a size 10 infant nasogastric feeding tube, which had been threaded down the umbilical vein ( Figure 4 ). To insert the tube, the vein can either be opened with a scalpel just outside the introitus or the cord can be re-cut and the nasogastric tube passed down the largest of the three exposed vessels until resistance is felt. The tube is then withdrawn by 5 cm to allow for any divisions of the vein prior to its insertion into the placenta. An alternative (and equally successful) method in vitro is to inject 30 mL directly into the cord and then ‘milk the cord’ so as to flush the solution up into the placenta. In clinical settlings, however, when the placenta is still intrauterine, the majority of the cord is intravaginal, making access to it for ‘milking’ difficult or impossible. The milking technique might therefore not produce the same success in practice as was achieved in the experiments. A further problem with the previous trials has been an inconsistency regarding the dose of oxytocin. Doses ranging from 10 to 100 iu have been tried. The published trials that have used higher dosages of oxytocin have, on the whole, found higher success rates ( Figure 5 ). A dose-comparison study in which 10, 30 and 50 iu were injected found that 50 iu improved the success rates without causing side effects (Weeks, unpublished). A large, placebo-controlled, randomised trial in which nearly 600 women were randomised to receive 50 iu oxytocin or saline using the Pipingas technique (the Release Trial) is due to be completed in late 2008. 36 Umbilical vein prostaglandin injection Two randomised trials have assessed the benefits of an intraumbilical prostaglandin injection. Bider et al randomised 17 women to receive prostaglandin F2α or saline and found that the technique was successful in all 10 of the women who received prostaglandin, whereas all 7 of those injected with saline alone required manual removal.11 Rogers et al compared the use of dissolved misoprostol tablets (800 μg in 30 mL saline) to oxytocin (50 iu in 30 mL saline) and to saline alone, all injected through the umbilical vein by the Pipingas technique. 37 They found success rates of 57%, 19% and 46%, respectively. The technique therefore shows promise, but more research is needed. Glyceryl trinitrate It has been suggested that many years that glyceryl trinitrate (GTN; its chemical name is nitroglycerine) might be effective for the management of RP. This was based on numerous observational studies, most of which used intravenous boluses of 50–200 μg. 38 Uterine relaxation occurs about 60 seconds after injection and lasts for 2 minutes. A randomised trial has now also demonstrated its efficacy. Bullarbo et al randomised 24 women to receive 1 mg GTN (or placebo) sublingually 20 minutes aftern an intravenous bolus of 10 units oxytocin. 39 The efficacy was 100% in those given GTN and only 8% in those treated with placebo ( P < 0.0001). Teatment with GTN also reduced the mean blood loss by nearly 300 mL. In those given GTN, the systolic blood pressure and diastolic BP dropped by a mean of 6 and 5 mmHg, respectively. Manual removal of placenta Adequate analgesia can be achieved through regional or general anaesthetic. MROP is best conducted in theatre, where aseptic technique is more easily achieved and where any complications (haemorrhage, placenta accreta or perforation) can be dealt with rapidly in association with the anaesthetist. After cleaning, draping and catheterising the woman, the surgeon should identify the interface between the uterus and maternal surface of the placenta by following the umbilical cord through the vagina. Once the rough, velvety interface between the uterus and placenta is identified, the plane is gently dissected using a side-to-side motion of the fingers. The other hand is used to steady the fundus of the uterus through the woman's abdomen. It is not unusual to find a small area where the placenta is very adherent to the uterus. This can usually be dealt with by patient, persistent working at the interface with the fingers, slowly identifying a plane of separation and easing the placenta away. The plane of dissection is often partially through the placenta at this stage, leaving some placenta adherent to the decidua and myometrium. This not a problem so long as the uterus can be sufficiently contracted afterwards to obstruct the blood flow through the radial arteries to the placental fragments. Sharp curettage should be avoided if possible as the myometrium might be very thin at the point of adherence and there is high risk of perforation. If the cervix is tightly closed when it comes to the MROP, uterine relaxation may be achieved with the aid of GTN in an IV bolus of 50–500 μg or 1 mg sublingually (see above). Marked uterine relaxation occurs after 30–40 seconds and the uterus recovers its tone after 1–2 minutes. MROP following either vaginal delivery or CS carries with it an increased risk of endometritis. 40,41 Full aseptic procedures should therefore be followed and a prophylactic broad-spectrum antibiotic used. Summary The incidence and importance of retained placenta (RP) varies greatly around the world. In less developed countries, it affects about 0.1% of deliveries but has up to 10% case fatality rate in rural areas. In more developed countries, it is more common (about 3% of vaginal deliveries) but very rarely associated with mortality. The difference in incidence might be due to its association with previous uterine surgery and labour induction. Although routine oxytocics for the prophylaxis of postpartum haemorrhage (PPH) decrease the median length of the third stage, they have no effect on the rate of retained placenta at 60 minutes (except for IV ergometrine, which increases the rate). There are three main types of retained placenta following the vagina delivery: placenta adherens (failed contraction of the myometrium behind the placenta), trapped placenta (a detached placenta trapped behind a closed cervix) and partial accreta (a small area of accreta preventing detachment). All can be treated by manual removal of placenta, which should be carried out at 30–60 minutes postpartum. Medical management is also an option for placenta adherens or trapped placenta. The need for manual removal can be reduced by 20% by the use of intraumbilical oxytocin (30 iu in 30 mL saline). A trapped placenta may respond to glyceryl trinitrate (500 mcg sublingually) or gentle, persistent, controlled cord traction. Practice points • The risk of retained placenta varies from 0.01 in less developed nations to 3.3% in more developed nations. • The mortality rate of this condition is up to 10% if left untreated. • The usual reason for retained placenta is failure of the retroplacental myometrium to contract, thus preventing detachment. • The risk of major haemorrhage rises after 30 minutes of placental retention. • Ultrasound can distinguish between a ‘trapped’ placenta and an ‘adherent’ placenta, allowing the former to be treated with GTN (two 400 μg puffs sublingually) and controlled cord traction. • For ‘adherent’ placentas injection of 30 iu oxytocin (in 30 mL saline) down the umbilical cord by the Papingas method is a worthwhile first-line option. • If this is unsuccessful after 30 minutes, then manual removal should be carried out under antibiotic cover. Research agenda • Does the underlying pathophysiology of RP vary according to region? • The accuracy of ultrasound in defining pathophysiological type of RP. • Do different types of RP respond differently to different types of management? • The value of medical management of RP using intraumbilical oxytocics, glyceryl trinitrate and intravenous prostaglandins. • Can medical managements be effectively given by community health workers in rural communities, and does this prevent maternal mortality? References *1 J.M. Munro Kerr Maternal mortality and morbidity 1933 E & S Livingstone Edinburgh pp 32–3 2 Confidential Enquiries into Maternal Deaths (CEMD) Why mothers die. 1997–1999 2001 RCOG Press London 3 J.E. Gordon H. Gideon J.B. Wyon Midwifery practices in rural Punjab, India Am J Obstet Gynecol 93 1965 734 742 4 K.A. Harrison Childbearing, health and social priorities: survey of 22,774 consecutive hospital births in Zaria, Northern Nigeria Br J Obstet Gynaecol 92 Suppl. 5 1985 100 115 5 A.D. Weeks F.M. Mirembe The retained placenta – new insights into an old problem (editorial) Eur J Obstet Gynecol Reprod Biol 102 2002 109 110 6 EUPHRATES Group (European Project on obstetric Haemorrhage Reduction: Attitudes, Trial and Early Warning System) European consensus on prevention and management of postpartum haemorrhage C. B-Lynch L.G. Keith A.B. Lalonde M. Karoshi A textbook of postpartum hemorrhage 2006 Sapiens Publishing Duncow 109 113 Available from: www.euphrates.inserm.fr 7 S. Hidar T.M. Jennane S. Bouguizane The effect of placental removal method at cesarean delivery on perioperative hemorrhage: a randomized clinical trial ISRCTN 49779257 Eur J Obstet Gynecol Reprod Biol 117 2 2004 179 182 *8 C.A. Combs R.K. Laros Prolonged third stage of labour: morbidity and risk factors Obstet Gynecol 77 1991 863 867 9 E.F. Magann S. Evans S.P. Chauhan The length of the third stage of labor and the risk of postpartum hemorrhage Obstet Gynecol 105 2 2005 290 293 *10 G. Carroli E. Bergel Umbilical vein injection for management of retained placenta Cochrane Database Syst Rev Issue 4 2001 10.1002/14651858.CD001337 Art. No.: CD001337 11 D. Bider M. Dulitzky M. Goldenberg Intraumbilical vein injection of prostaglandin F2alpha in RP Eur J Obstet Gynecol Reprod Biol 64 1996 59 61 *12 National Collaborating Centre for Women's and Children's Health (NCCWCH) Intrapartum care. Care of healthy women and their babies during childbirth 2007 RCOG Press London 13 WHO Pregnancy, childbirth, postpartum and newborn care: a guide for essential practice pp B11 2nd edn. 2006 WHO Geneva *14 W.J. Prendiville D. Elbourne S. McDonald Active versus expectant management in the third stage of labour Cochrane Database Syst Rev Issue 3 2000 10.1002/14651858.CD000007 Art. No.: CD000007 15 J. Rogers J. Wood R. McCandlish Active versus expectant management of third stage of labour: the Hinchingbrooke randomised controlled trial Lancet 351 1998 693 699 16 D.A. Miller J.A. Chollet T.M. Goodwin Clinical risk factors for placenta previa-placenta accreta Am J Obstet Gynecol 177 1997 210 214 17 Palcaios Jaraquemada JM. Diagnosis and management of placenta accreta. Best Pract Res Clin Obstet Gynaecol. *18 M.H. Hall R. Halliwell R. Carr-Hill Concomitant and repeated happenings of complications of the third stage of labour Br J Obstet Gynaecol 92 1985 732 738 19 B. Adelusi M.H. Soltan N. Chowdhury Risk of retained placenta: multivariate approach Acta Obstet Gynecol Scand 76 1997 414 418 20 C.M. Begley A comparison of ‘active’ and ‘physiological’ management of the third stage of labour Midwifery 6 1990 3 17 21 M. Hammar K. Boström B. Borgvall Comparison between the influence of methylergometrine and oxytocin on the incidence of retained placenta in the third stage of labour Gynecol Obstet Invest 30 1990 91 93 22 L.K. Green R.E. Harris Uterine abnormalities. Frequency of diagnosis and associated obstetric complications Obstet Gynecol 47 1976 427 429 23 A. Golan A. Raziel M. Pansky Manual removal of the placenta - its role in intrauterine adhesion formation Int J Fertil Menopausal Stud 41 1996 450 451 *24 A. Herman Z. Weinraub I. Bukovsky Dynamic ultrasonographic imaging of the third stage of labor: new perspectives into third stage mechanism Am J Obstet Gynecol 168 1993 1496 1499 25 T.W. Deyer J.A. Ashton-Miller P.M. Van Baren Myometrial contractile strain at uteroplacental separation during parturition Am J Obstet Gynecol 183 2000 156 159 26 A.D. Weeks The retained placenta J. Studd Progress in obstetrics and gynaecology vol.16 2004 Churchill Livingston Edinburgh 27 A.D. Weeks Placental influences on the rate of labour progression: a pilot study Eur J Obstet Gynecol Reprod Biol 106 2003 158 159 28 H. Soltani F. Dickinson I. Symonds Placental cord drainage after spontaneous vaginal delivery as part of the management of the third stage of labour Cochrane Database Syst Rev Issue 4 2005 10.1002/14651858.CD004665.pub2 Art. No.: CD004665 29 G. Peña-Martí G. Comunián-Carrasco Fundal pressure versus controlled cord traction as part of the active management of the third stage of labour Cochrane Database Syst Rev Issue 4 2007 10.1002/14651858.CD005462.pub2 Art. No.: CD005462 30 J.M. Nardin G. Carroli A.D. Weeks Umbilical vein injection for the routine management of third stage of labour. (Protocol) Cochrane Database Syst Rev Issue 4 2006 10.1002/14651858.CD006176 Art. No.: CD006176 31 S. Kore S. Srikristna A. Hedge Active management of third stage of labour with intraumbilical oxytocin injection J Obstet Gynaecol India 50 2000 54 55 32 C.H. Bullough R.S. Msuku L. Karonde Early suckling and postpartum haemorrhage: controlled trial in deliveries by traditional birth attendants Lancet 8662 1989 522 525 33 A.M. Gulmezoglu J. Villar N.T. Ngoc WHO multicentre randomised trial of misoprostol in the management of the third stage of labour Lancet 358 9283 2001 689 695 34 H.J. van Beekhuizen A.N. de Groot T. De Boo Sulprostone reduces the need for the manual removal of the placenta in patients with retained placenta: a randomized controlled trial Am J Obstet Gynecol 194 2 2006 446 450 *35 A. Pipingas G.J. Hofmeyr K.R. Sesel Umbilical vessel oxytocin administration for retained placenta: in-vitro study of various infusion techniques Am J Obstet Gynecol 168 1993 793 795 *36 A. Weeks F. Mirembe Z. Alfirevic The release trial: a randomised controlled trial of umbilical vein oxytocin versus placebo for the treatment of retained placenta BJOG 112 10 2005 1458 37 M.S. Rogers P.M. Yuen S. Wong Avoiding manual removal of placenta: evaluation of intra-umbilical injection of uterotonics using the Pipingas technique for management of adherent placenta Acta Obstet Gynecol Scand 86 1 2007 48 54 38 P. Dufour D. Vinatier F. Puech The use of intravenous nitroglycerin for cervico-uterine relaxation: a review of the literature Arch Gynecol Obstet 261 1 1997 1 7 39 M. Bullarbo J. Tjugum E. Ekerhovd Sublingual nitroglycerin for management of retained placenta Int J Gynaecol Obstet 91 3 2005 228 232 Erratum in: Int J Gynaecol Obstet. 2006; 92(3): 337 40 M.W. Atkinson J. Owen A. Wren The effect of manual removal of the placenta on post-cesarean endometritis Obstet Gynecol 87 1996 99 102 41 J.W. Ely A. Rijhsinghani N.C. Bowdler The association between manual removal of the placenta and postpartum endometritis following vaginal delivery Obstet Gynecol 86 1995 1002 1006 42 S. Chhabra M. Dhorey Retained placenta continues to be fatal but frequency can be reduced J Obstet Gynaecol 22 6 2002 630 633 43 U. Onwudiegwu O.N. Makinde Retained placenta: a cause of reproductive morbidity in Nigeria J Obstet Gynaecol 19 4 1999 355 359 44 K.A. Harrison Mode of delivery with notes on rupture of the gravid uterus and vesicovaginal fistula Br J Obstet Gynaecol 92 Suppl. 5 1985 61 71 45 E. Sheiner A. Levy M. Mazor Precipitate labor: higher rates of maternal complications Eur J Obstet Gynecol Reprod Biol 116 1 2004 43 47 *46 M.P. Dombrowski S.F. Bottoms A.A. Saleh Third stage of labor: analysis of duration and clinical practice Am J Obstet Gynecol 172 1995 1279 1284 47 H. Titiz A. Wallace D.C. Voaklander Manual removal of the placenta–a case control study Aust N Z J Obstet Gynaecol 41 1 2001 41 44 48 W. Zhou G.L. Nielsen H. Larsen Induced abortion and placenta complications in the subsequent pregnancy Acta Obstet Gynecol Scand 80 2001 1115 1120 49 L. Calderdale N.F. Dalle R. Franzoi Éutile la somministrazione di ossitocina nella vena ombilicale per il trttamento della placenta ritenuta? G Ital Ostet Ginecol 16 5 1994 283 286 Quoted in: Carroli G, Bergel E. Umbilical vein injection for management of retained placenta. Cochrane Database Syst Rev 2001, Issue 4. Art. No.: CD001337. DOI: 10.1002/14651858.CD001337 50 P. Hansen L. Jorgensen M. Dueholm Intraumbilical oxytocin in the treatment of retained placenta Ugeskr Laeger 149 1987 3318 3319 Quoted in: Carroli G, Bergel E. Umbilical vein injection for management of retained placenta. Cochrane Database Syst Rev 2001, Issue 4. Art. No.: CD001337. DOI: 10.1002/14651858.CD001337 51 J.M. Frappell J.M. Pearce P. McParland Intra-umbilical vein oxytocin in the management of retained placenta: a random, prospective, double blind, placebo controlled study J Obstet Gynaecol 8 1988 322 324 52 M.G.P. Huber H.I.J. Wildschut K. Boer Umbilical vein administration of oxytocin for the mangement of retained placenta: it is effective? Am J Obstet Gynecol 164 1991 1216 1219 53 M. Selinger I.Z. Mackenzie P. Dunlop Intra-umbilical vein oxytocin in the management of retained placenta. A double blind placebo controlled study J Obstet Gynaecol 7 1986 115 117 54 F.V. Kristiansen L. Frost P. Kaspersen The effect of oxytocin injection into the umbilical vein for the management of retained placenta Am J Obstet Gynecol 156 1987 979 980 55 M.R. Gazvani M.J.M. Luckas A.J. Drakeley Intraumbilical oxytocin for the management of retained placenta: a randomized controlled trial Obstet Gynecol 91 1998 203 207 56 G. Carroli J.M. Belizan A. Grant For the Grupo Argentino de Estudio de Placenta Retenida. Intra-umbilical vein injection and retained placenta: evidence from a collaborative large randomised controlled trial Br J Obstet Gynaecol 105 1998 179 185 57 C. Wilken-Jensen V. Strom M.D. Nielsen Removing placenta by oxytocin - a controlled study Am J Obstet Gynecol 161 1989 155 156