A Recurring Pregnancy Complication

A Recurring Pregnancy Complication

Michelle A. Kominiarek, MD,* and Sarah J. Kilpatrick, MD, PhD †

Postpartum hemorrhage (PPH) is a potentially life-threatening complication of both vaginal and cesarean deliveries. Although many variables increase the chance for bleeding, a PPH in a previous pregnancy is one of the greatest risk factors for recurrent PPH. A physiologic explanation for this association is not known, but recurrent risk factors such as a retained placenta or underlying medical disorders may account for the majority of recurrent PPH cases. To reduce maternal morbidity and mortality, prevention of PPH in these patients is critical. Steps to minimize hemorrhagic complications include the identification of high-risk patients through a complete history, vigilant management of the third stage of labor, and having uterotonic medications readily available in the delivery room. Patients with inherited coagulopathies require individualized treatment, and their risks for bleeding extend beyond the first 24 hours after delivery. Further studies are needed to determine whether the administration of prophylactic measures such as prostaglandins decrease the PPH occur- rence in high-risk patients. Semin Perinatol 31:159-166 © 2007 Elsevier Inc. All rights reserved.

KEYWORDS postpartum hemorrhage, recurrence, risk factors, prevention, retained placenta, coagulation disorders

A blood cell transfusion occurs in less than 1% and after a

lthough the prevalence of postpartum hemorrhage

(PPH) varies between developing and developed coun-

cesarean delivery 1% to 7%. 4

tries, it is the leading cause of maternal morbidity and mor- Late or secondary PPH is excessive vaginal bleeding occur- tality worldwide. 1 The etiology of PPH falls into four main

ring between 24 hours and 6 weeks after delivery. 5 Unlike the categories: tone, tissue, trauma, and thrombosis disorders

quantitative definition of primary PPH, the definition of sec- ( Table 1 ).

ondary PPH is more subjective and requires sufficient bleed- An estimated blood loss ⬎500 mL for a vaginal delivery

ing to prompt the patient to seek medical attention. Second- and ⬎1000 mL for a cesarean delivery defines early or pri-

ary PPH is also referred to as persistent or delayed PPH and is mary PPH, which occurs within the first 24 hours after de-

estimated to occur in 1% to 3% of all deliveries. 6 Patients livery. This affects 4% to 6% of pregnancies, and uterine

usually present during the second postpartum week, and the

atony is the cause in 75% to 90% of cases. 2,3

most common etiology is retained placenta fragments. description of blood loss at delivery limits the interpretation

The subjective

Although PPH occurs in women without risk factors, it is of outcomes in any study of PPH. Comparisons of pre- and

often a predictable event. There are many risk factors sug- postpartum hemoglobin or hematocrit may be more accu-

gested for PPH ( Table 2 ). These include an over-distended rate, and a decrease in hematocrit levels by 10% has also

uterus (multiple gestations, polyhydraminos, macrosomia), defined PPH. 2 Although a patient may meet blood loss crite-

primigravidity, chorioamnionitis, prolonged rupture of ria for a PPH, blood transfusion rates are better estimates of

membranes, fibroids, previous cesarean delivery, coagulation the hemorrhage severity. Postpartum anemia resulting in red

disorders, anticoagulant therapy, labor induction and augmen- tation, prolonged labors, preeclampsia, obesity, and general an-

*Department of Obstetrics and Gynecology, Indiana University School of

esthetics. 7-9 The relationship between grand multiparity (ⱖ5

Medicine, Indianapolis, IN.

vaginal births) and PPH has been disputed. 2,3,8,10,11 In a univar-

†Department of Obstetrics and Gynecology, University of Illinois at Chi-

iate analysis, delivery by a midwife was associated with a de-

cago, Chicago, IL. creased risk of PPH compared with physician deliveries. Address reprint requests to Michelle A. Kominiarek, MD, 550 North Uni- 2

versity Boulevard, Room 2440, Department of Obstetrics and Gynecol-

One of the most important risk factors for PPH is a prior

ogy, Indianapolis, IN 46202. E-mail: mkominia@iupui.edu

PPH. However, in women without recurrent risk factors,

0146-0005/07/$-see front matter © 2007 Elsevier Inc. All rights reserved.

doi:10.1053/j.semperi.2007.03.001

160 M.A. Kominiarek and S.J. Kilpatrick

Table 1 Etiology of Postpartum Hemorrhage Hall and coworkers to study the recurrence risk for either Tone

PPH (ⱖ500 mL blood loss at a singleton vaginal delivery) or Uterine atony

retained placenta (requiring manual removal) using a longi- Uterine inversion

tudinal analysis which controlled for the patient’s reproduc- Tissue

tive history. 11 The population included 6615 women who Retained placenta or blood clots

delivered between 1967 and 1981. Although the original Abnormal placentation (previa, accreta)

paper did not reports statistics, for patients with two consec- Connective tissue disorders (Ehlers-Danlos, Marfans)

utive live births and a history of PPH in the first birth, the Trauma

odds ratio (OR) for a patient to have a subsequent PPH was Lower genital tract lacerations

3.68 (95% CI 2.49-5.45). Interestingly, after a labor induc- Thrombosis disorders

Uterine rupture

tion for the second birth, the risk of either recurrent PPH or Coagulopathies

retained placenta was also significant at 19.6% (OR 2.89, Inherited coagulation disorders

95% CI 2.89-5.28). Of 1106 women who had three consec- HELLP

utive live births, only one had a PPH three times. PPH oc- DIC

curred in 13.5% in the second live birth in 375 women whose Anticoagulant use

first birth was preceded by an abortion. In summary, the incidence of PPH and/or retained placenta in the next two births was ⬎12% in the presence of a PPH and/or retained placenta in the first birth. If there was no prior history of PPH

such as a previous twin gestation or chorioamnionitis, the or retained placenta, the incidence of either one in the sub- physiological explanation for the increased recurrence is un-

sequent pregnancy was ⬍6% unless there was an intervening known. The focus of this article is to review data on the

abortion. 11 Although this study did not address pregnancy recurrence of either primary or secondary PPH in future

complications or risk factors, patients with a prior PPH or pregnancies.

retained placenta were more likely to have a recurrence. In a more recent case-control study of risk factors for PPH,

The Epidemiology

a previous PPH had an OR of 3.55 (95% CI 1.24-10.19) for

of Recurrent PPH recurrent PPH (a hematocrit decrease of ⱖ10 points between

admission and postdelivery or by the need for blood transfu- The objective of one of the earliest studies on recurrent PPH

sion) in a multivariate analysis. 2 A previous PPH was one of was to determine whether a patient with a prior PPH was

the strongest predictors of recurrent PPH in their 17-factor more likely to hemorrhage during or after the third stage of a

logistic regression model. An interesting aspect of the study subsequent labor. They included deliveries from 1936 to

was their analysis of which hemorrhages might be predict- 1945 and defined PPH as an estimated blood loss ⬎600 mL. 3

able. A regression model of variables potentially known be- Of interest, cesareans, which were excluded from the analy-

fore the onset of labor, such as preeclampsia, parity, multiple sis, accounted for only 1.7% of the deliveries. Of the 12,243

gestation, prior PPH, or previous cesarean delivery, derived women with vaginal births, the rate of PPH was 5.2%. How-

an adjusted OR for a previous PPH of 2.85 (95% CI 1.07- ever, the recurrence rate of PPH was 8.1%. In 68% (21/31) of

7.60). Similar results were reported in a review of 19,476 the repeated PPH cases, the cause was the same as the initial

deliveries at a tertiary care center. PPH (blood loss ⬎1000 mL hemorrhage, suggesting that recurrent risk factors may play a role in PPH recurrence. 3

Table 2 In a study of recurring abnormalities of the third stage of Risk Factors for Postpartum Hemorrhage labor, 132 pregnancies with a known prior PPH were evalu-

Non-recurring

ated. 12 Twenty-three percent had a recurrent PPH (blood loss

Primigravidity

⬎20 oz or required placenta extraction), and 22% had a

Macrosomia

“potentially” abnormal third stage but precautions were

Polyhydraminos

taken to prevent hemorrhage (placenta removed or given Multiple gestations Prolonged or augmented labors

ergometrine even though blood loss was ⬍20 oz). After one Prolonged third stage PPH, there was a recurrence in 20/100 (20%) and in 7/25

Chorioamnionitis

(28%) after more than one PPH. Even if a normal third stage Antepartum hemorrhage accompanied a second pregnancy following a prior PPH, the

Operative deliveries

occurrence of PPH in the third pregnancy was still high, at

Recurring

21%. There was a subset of 10 women whose risk factors for

Fibroids

PPH in the first pregnancy included nonrecurring complica-

Maternal obesity

tions such as general anesthesia, antepartum hemorrhage, Coagulation disorders and multiple gestations. These women had a total of 17 sub-

Previous cesarean sequent pregnancies without PPH. 12 Specific medical/genetic disorders

Changes in obstetrical practice, including routine use of

ⴞGrand multiparity Previous postpartum hemorrhage

oxytocics and decreasing parity among women, prompted

Postpartum hemorrhage 161

Table 3 Recurrence Risk for Postpartum Hemorrhage Based ery. 15 Although the numbers in this report are small, it is the on Prior History and Risk Factors

largest series of pregnancies reported after hypogastric artery

Recurrence

ligation, and a recurrence of 3/13 (27%) is significant.

Several studies have addressed the long-term effect of uterine Primary PPH 3,11,12

Risk Factor

Risk for PPH

8-28%

artery embolization (UAE) for the control of PPH on menses,

fertility, and future pregnancies. Thirteen full-term deliveries Prior PPH treated with hypogastric artery

Secondary PPH 14 19%†

after a previous bilateral UAE for a PPH were uncomplicated, ligation 15

and no instances of recurrent PPH were reported. 16,17 Prior PPH treated with uterine artery

In both of these studies, the authors do not mention the embolization 16-18

0-100%

etiology or any high-risk factors for hemorrhage in the prior Myomectomy as treatment for

0-1%

pregnancy or if any prophylactic measures were taken to prevent a recurrence. In contrast to these reassuring out-

fibroids 29,31

Uterine artery ligation as treatment for

fibroids 21,29,30,32,33 comes, a separate study describes four patients who delivered

6-19%

Von Willebrand disease 46 80%

at term after a UAE for PPH in a prior pregnancy. Hemor- rhage recurred in all of them, and two required a hysterec-

ⴱBaseline risks: primary PPH 4-6%, secondary PPH 1-3%. †Risk is for recurrent secondary PPH.

tomy for placenta accreta. 18 The etiology for the prior PPH was uterine atony in three cases and a placenta accreta in the fourth. There are case reports of successful pregnancy out-

comes without hemorrhage after a B-lynch suture 19 and a and/or need for blood transfusion) occurred in 5.15% of

B-lynch suture combined with hypogastric artery ligation. 20 vaginal deliveries and a prior PPH had an OR of 2.2 (95% CI 1.7-2.9) for recurrent PPH. 13

The small number of cases limits the interpretation of these studies. The exact cause for the recurrent PPH is unclear, but

a devascularized myometrium after UAE may not allow the been described for secondary PPH. A retrospective study

Although data are more limited, recurrent PPH has also

uterus to adequately contract after a delivery. 21 Other theo- from two hospitals in the United Kingdom identified 48 cases

ries propose that a prior UAE may lead to abnormal implan- of secondary PPH (0.73% incidence). Of the 32 multiparas, 6

tation and excessive trophoblast invasion in future pregnan- (18.8%) also had a secondary PPH in a previous pregnancy. 14 cies. 18 It may be reasonable to consider antenatal imaging in

Over several decades, despite changing obstetrical care, a these cases to assess the placental implantation site for evi- previous PPH remains an important predictor of PPH in sub-

dence of invasive placental disease. Although outcomes are sequent deliveries. Clinicians should consider it as one of the

mixed, preparation for the recurrence of PPH and placenta most important risk factors for PPH ( Table 3 ).

accreta is the best approach in these patients.

Condition-Specific

Fibroids

Recurrence Risks for

Fibroids may increase the chance for PPH. The mechanism

Postpartum Hemorrhage

may be mediated through abnormal muscle contractility leading to uterine atony. Although they have been cited as the

Previous Invasive Treatment for PPH

cause for many complications in pregnancy, including pre- The primary management of PPH is medical: treatment with

term labor, abruption, fetal growth restriction, dysfunctional uterotonic drugs. In most cases, this is successful; however,

labor, and cesarean delivery, the studies regarding fibroids surgical techniques to control bleeding, such as hypogastric

and PPH are conflicting, where some show an increased risk 22-25 and others show no association. artery ligation, bilateral uterine artery ligation (O’Leary su- 26-28 tures), and the B-Lynch technique, are alternatives to hyster-

Although no investigations have directly evaluated the ectomy in cases of persistent bleeding. Arterial embolization

PPH recurrence in the setting of uterine fibroids, a number of or balloon occlusion of radiographically identified bleeding

studies have described PPH outcomes in patients treated with vessels is another nonsurgical option for continued hemor-

either an interval myomectomy or UAE for symptomatic fi- rhage. Patients requiring any of these treatments for either a

broids. In an analysis of 50 published cases of pregnancy after primary or secondary PPH were very likely to have suffered a

UAE for fibroids, there were 2/23 (9%) occurrences of PPH. 21 significant hemorrhage. The risk for recurrent PPH is of ut-

In a subsequent study, these authors compared pregnancy most concern in this group of patients.

outcomes in women treated with UAE to laparoscopic myo- Nizard and coworkers reported subsequent pregnancy

mectomy. The difference in the PPH rates did not reach sta- outcomes after bilateral hypogastric artery ligation in 43

tistical significance: 6% versus 1% (OR 6.3, 95% CI 0.6-71.8) women. 15 Information was obtained either through chart re-

for the UAE and myomectomy groups, respectively. 29 A sim- view or telephone interview. Of the 13 completed pregnan-

ilar study surveyed women who became pregnant after a UAE cies, two had a “threatened” PPH which was described as

for fibroids. Of the 26 pregnancies, 16 continued beyond the “easily managed by manual evacuation of the placenta and

second trimester with a PPH rate of 19%. 30 A review of 158 intravenous oxytocin,” and one patient had a PPH success-

pregnancies after laparoscopic myomectomy reported no fully treated with prostaglandins during a cesarean deliv-

cases of PPH, even though the cesarean delivery rate was

162 M.A. Kominiarek and S.J. Kilpatrick

75%. 31 Walker and coworkers described 56 completed preg- indications to vaginal delivery, then this should be the pre- nancies after UAE with 6 cases (18.2%) of PPH, which was

ferred route, but the placenta should be delivered without similar to the 3/18 (17%) rate of PPH described in the On-

excessive cord traction.

tario Multicenter Trial, a large prospective study of women undergoing UAE as an alternative to hysterectomy for symp-

Von Willebrand Disease

tomatic fibroids. 32,33 The recurrence of PPH in patients treated with either myo-

A maternal coagulation disorder increases the risk for PPH. mectomy or UAE is difficult to interpret from these small

Von Willebrand disease (VWD), the most common inherited retrospective studies as the previous pregnancy outcomes

bleeding disorder, is found in 1% of the general population were not compared and PPH was not always defined. How-

regardless of ethnicity. Of the three categories, type 1 ac- ever, the available data suggest that the risk for PPH after

counts for 70% of all cases. Although factor VIII and von myomectomy is less than it is after UAE. Clearly, the removal

Willebrand factor antigen (vWF:Ag) levels often improve in or treatment of fibroids before pregnancy does not eliminate

pregnancy, women with VWD are at increased risk for PPH the risk of PPH, and in some instances, it appears to be

because of the rapid decline in these levels after delivery. increased.

Rates have been estimated as high as 16% to 29% for primary PPH and 20% to 28% for secondary PPH, 41-43 and transfusion

rates as high as 25% have been reported. 44 Retained Placenta PPH occurs more

commonly in type 2 and 3 patients and those with vWF:Ag The incidence of retained placenta is 1% to 5.5%. The occur-

levels ⬍50% of normal at term. 41,45 rence of PPH is significantly higher when there is a retained

Of 75 women with type I VWD followed at 46 different placenta: 9.6% to 21.3% versus 2.3% to 3.5%. Retained

hemophilia treatment centers in the United States, 32% re- placenta is essentially another complication of the third stage

ported PPH a total of 54 times, suggesting a high recurrence of labor, and many studies suggest that it is likely to recur in

rate in subsequent pregnancies. 44 PPH recurred with succes- future pregnancies. The medical records of 24,750 deliveries

sive pregnancies in 80% of patients who had type I VWD in over an 8-year period at a hospital in Norway were reviewed.

combination with PPH during the first birth. 46 In summary, 165 women (0.6%) had a manual placenta re-

34 moval, and PPH occurred in 16 (10%). Kadir and coworkers described 67 women with VWD fol- Of the 74 parous lowed at the Royal Free Hospital Hemophilia Centre from women, 12 (16%) had a prior retained placenta. A similar

1980 to 1996. 44 The diagnosis of VWD was unknown in six study of 134 patients with a retained placenta reported re-

women with 11 pregnancies, and the diagnosis was later

established in two women when PPH occurred after an abor- 113 women with a retained placenta, a prior retained pla-

currences in 23% to 32% of cases. 35 In a case-control study of

tion. In an analysis of 38 women with type I VWD, the diag- centa was a risk factor for recurrence, OR 9.8 (95% CI 1.1-

36 85.5) in a logistic regression analysis. nosis of VWD was unknown before presentation in a sub- Although recurrence stantial number of cases, including 5 (13.1%) with PPH. 47 of PPH has not been included in these reports, it is appropri-

This information leads one to question whether a patient’s ate to conclude that a history of retained placenta is a risk for

PPH is the consequence of an undiagnosed coagulation dis- its recurrence and, therefore, PPH.

order such as VWD. The purpose of the study by Hundegger and coworkers was to retrospectively evaluate patients with

Uterine Inversion

PPH, defined as a drop in hemoglobin concentration of at Uterine inversion, a potentially life-threatening complication

least 8% between delivery day and postpartum day 3, for type of the third stage of labor, is associated with PPH in 94% of

1 VWD. 48 Of the 3565 women who delivered in 1997, 14 cases. 37,38 In most situations, appropriate management of the

women were eligible after excluding cesarean deliveries and third stage can prevent this occurrence. Because it compli-

major birth injuries. These patients were contacted by phone cates few deliveries (about 1 in 2,500), the recurrence of

and returned for testing after stopping estrogen-containing uterine inversion is difficult to quantify. A review of 56 preg-

hormones for 2 months and aspirin and nonsteroidal antiin- nancies after a previous uterine inversion from various re-

flammatory drugs for 1 week. Blood samples, collected on ports suggested that it recurred in 33% of subsequent preg-

days 5 to 7 of the menstrual cycle, were tested for vWF:Ag, nancies. 39 All recurrences were in those patients who did not

factors II, V, VII, VIII, IX, X, XI, and XII, prothrombin, acti- have surgery (Spinelli operation, Piccoli’s incision, combined

vated partial thromboplastin time (aPTT), thrombin time, Piccoli-Borelius-Westermann method, Küstner operation,

fibrinogen, and for a complete blood count. None had abnor- Küstner-Borelius-Westermann operation, Hehrer’s method,

mal levels of vWF:Ag or other factor levels. 48 Although the Duret’s Method, or Aveling repositor) to correct the inver-

numbers are small, this is the only study that evaluated pa- sion. In contrast, a more recent review of 40 cases of uterine

tients for a coagulation disorder after having a PPH. The inversion where PPH and blood transfusion rates were 65%

prevalence of undiagnosed VWD in women with PPH is pres- and 47.5%, respectively, reported no recurrences of uterine

ently unknown.

It is critical that the obstetrician/gynecologist is aware of ommended delivery route for patients with a prior uterine

inversion in 26 subsequent pregnancies. 40 Although the rec-

the prevalence and clinical presentation of patients with inversion has never been described in the literature, recur-

VWD. At the first prenatal visit or after a pregnancy-related rent uterine inversion is a rare event. If there are no contra-

hemorrhage, it is necessary to obtain a bleeding history, es- hemorrhage, it is necessary to obtain a bleeding history, es-