who chapter 8 intrauterine fetal death 27022007[final]

7/28/2019 WHO Chapter 8 Intrauterine Fetal Death 27022007[Final]

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Second and third trimester intrauterine fetal deathWHO misoprostol guidelines

Draft 2/26/07, Page 1

CHAPTER 8: INTRAUTERINE FETAL DEATH

AUTHORS:Rodolfo Gomez,Deborah Wing,Christian Fiala

INTRODUCTION

The frequency of intrauterine fetal death with a retained fetus varies but isestimated to occur in 1% of all pregnancies. This clinical situation ispsychologically stressful for the woman and her family members, and for thehealth professionals providing care.

When a fetus dies in uterus, the options for health care are either to awaitonset of spontaneous labor or to induce labor (Silver, 2007). The vast majority(over 90%) of women will have labor and deliver within three weeks of theintrauterine death. Expectant management remains an acceptable option insome settings for this diagnosis. In cases where expectant management ischosen, the clinical concern will be the development of disseminatedintravascular coagulation with its inherent risks of haemorrhage, blood producttransfusion and maternal death.

As induction of labor is a common and evidence based practice ofobstetrics, in cases of intrauterine fetal death (IUFD), the choice to induce laborin a patient with ripe cervix is straightforward and the procedure oftenuncomplicated. But the complexity in medical management increasessignificantly when the cervix is unripe or unfavourable (Bishop score < 6).Inducing labor in a pregnant woman with an unripe cervix is associated withfailed induction of labor and a higher risk of caesarean delivery. This problem hasbeen dramatically reduced with the local or systemic use of prostaglandins andother mechanical methods of cervical ripening prior to intravenous oxytocinadministration for labor induction. There is no gold standard, either medical orsurgical, for treatment of late IUFD.

Oral misoprostol administration for labor induction with an IUFD was firstdescribed in Sao Paulo, Brazil in 1987 (Mariani-Neto, 1987). Since that time,misoprostol use for obstetrical purposes has grown widely. There are dozens of

reports, many policy statements, reviews, and meta-analyses describing its usefor induction with live fetuses. Unfortunately, there is lack of uniformity in thedose and frequency of misoprostol dosing when used for induction of labor in thesecond and third trimester, and very few good quality randomized controlled trialsfor its use in IUFD.

The issues related to proper use of misoprostol are somewhat different forwomen who have need for labor induction in the face of IUFD compared to thosewith live fetuses. This is because the issues related to fetal wellbeing are


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eliminated; however, the possibility of disseminated intravascular coagulationcomplicating IUFD jeopardizes the womens life. The concerns regarding otherside effects such as uterine overactivity (hyperstimulation, hypertonus andtachysystole) and systemic response (nausea, vomiting, diarrhea and shivering),as well as safety remain with the use of misoprostol for labor induction with IUFD

as in cases where misoprostol is used for induction with live fetuses.For induction for IUFD, vaginal misoprostol is as effective as dinoprostone(Jain 1994) and gemeprost (Eng 1997), and less costly. The additional use ofcervical laminaria with misoprostol does not increase its efficacy (Jain 1996)(Level I), but pre-induction administration of oral mifepristone shortens the timeneeded for labor induction (Wagaarachi 2002, Fairley 2005). Mifepristone is,however, not widely available.

There is a limited high quality and homogeneous evidence base in peer-reviewed journals for misoprostol use for labor induction with IUFD (Neilson,2006, Clark, 2007). The vast majority of reports are descriptive series or non-randomized prospective comparisons. Cases series report shorter time until

delivery and lower doses required of misoprostol to obtain success in cases ofIUFD compared with live fetuses (Srisomboon 1998, Dodd 2005). There is awealth of data for second trimester pregnancy termination which are useful andcan be applied to IUFD in the second trimester (Clark, 2007). Similarly, data forlabor induction with live fetuses can be applied to IUFD in the third trimester(Hofmeyr 2003). Further research specifically for both second and third trimesterlabor induction with IUFD is needed.

DEFINITIONS

Intrauterine fetal death (IUFD): Intrauterine pregnancy beyond 12 weeks with a

dead fetus, which has not been expelled.

Disseminated intravascular coagulation: A consumptive coagulopathyoccasionally seen in conjunction with second or third trimester intrauterine fetaldeath.

INDICATIONS

Vaginally applied misoprostol for cervical ripening and labor induction isindicated in all cases of IUFD with a retained fetus and an unfavourable cervix.This is true regardless of stage of the pregnancy, as long as there is no

contraindication for vaginal delivery or misoprostol use. Although indicated at anygestational age, it is particularly useful in the second trimester (defined as 13 to26 weeks), when uterine evacuation often proves more difficult due to themyometrium's low responsiveness to oxytocin, lack of ready availability ofsurgical methods, and the risks associated with these surgeries.


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CONTRAINDICATIONS

Allergy to prostaglandins and contraindications to vaginal delivery. Thelatter includes placenta previa and transverse lie, although in thosecircumstances where placenta previa and malpresentation complicate IUFDs up

to 24 weeks, it may be appropriate to use misoprostol, depending on the skills ofthe health care providers and the setting.

PRECAUTIONS

When vaginal misoprostol is used for induction in a woman with a livefetus and a history of prior caesarean or uterine surgery, there is an increasedrisk of uterine rupture. The majority of studies of induction using misoprostol forsecond and third trimester IUFD, however, did not include women with previousuterine scars from Caesareans (Jain 1994, Jain 1996, Srisomboon 1998, Hidar2001, Makklouf 2003, Fadalla 2004, Niromanesh 2005,), But in the studies in

which they were included there were no cases of uterine rupture, including duringearly second trimester (Nakintu 2001, Rouzi 2003, Caliskan 2005, Dodd 2005)Herabutya 2003, Pongsatha 2004, Dickinson 2005, Daponte 2006). In womenwith previous cesarean births, lower doses should be used and doublingshould not occur

Surveillance for disseminated intravascular coagulation should occur,although the consumption of coagulation factors is a gradual process that usuallyoccurs over weeks after the fetal death. If the patient has disseminatedintravascular coagulation, blood transfusion should be given to correct thecoagulopathy prior to the induction.

REGIMEN

The spectrum of dosing regimens for vaginal misoprostol administrationdescribed in the literature for cervical ripening and induction of labor for secondand third trimester IUFD range from 50 to 400 micrograms given every 3 to 12hours by various routes of administration. All have been shown to be clinicallyeffective. Nevertheless, the current evidence base supports the conclusion thatthe most appropriate application is per vagina (Jain 1994, Fletcher 1996, Yapar1996, Nakintu 2001, Wagaarachi 2002, Chittacharoen 2003, Hofmeyr 2003,Fawole 2004, Nyende 2004, Pongsatha 2004, Dodd 2005, Niromanesh 2005).(Level I, strong recommendation)

For IUFD from 13 to 26 weeks (Jain 1994, leRoux 2001, Dickinson 2003,Hofmeyr 2003, Ngai 2003, Fadalla2004, Niromanesh 2005)

Place tablet deep within the vagina. Start with doses of:

o 200 mcg if fetal death occurred between 13 and 17 weeks'

gestation. (Level I, strong recommendation)o 100 mcg if fetal demise occurred between 18 and 26 weeks'

gestation. (Level I, strong recommendation)


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o Repeat the dose every 6 to12 hours for a total of 4 doses.(Level

I, strong recommendation) If the firstdose does not lead toeffective contractions the subsequent dose could be doubled asfollows:

o 13 to 17 weeks: 400 mcg

o 18 and 26 weeks: 200 mcg (Level IV)o The maximum daily dosing should not exceed:



For IUFD beyond 26 weeks (Bugalho 1994, Hofmeyr 2003, Chittacharoen 2003,Nakintu 2001, Nyende 2004, Fawole 2005)

If the cervix is unripe, insert 25 to 50 mcg of misoprostol into the

posterior vaginal fornix. If necessary, repeat every 4 hours (Level I,strong recommendation).If the first dose does not lead to effectivecontractions the subsequent dose could be doubled to 50 or 100 mcg

(Level IV).o The maximum daily dosing should not exceed: 600 mcg

If expulsion has not occurred the same treatment can be repeated the

following day.o Oxytocin administration, if necessary, may begin after 4 hours

following administration of the last dose of misoprostol.

COURSE OF TREATMENT

Effectiveness

Regardless of route of misoprostol administration, the vast majority ofwomen (67-83%) with late IUFD will deliver vaginally within 24-hours (Jain 1994,Draycott 1996, Nakintu 2001, Chittacharoen 2003, Nyende 2004, Dodd 2005,).(Level I) The remainder will deliver within the ensuing additional 24-hours(Mariani-Neto 1987, Jain 1994, Draycott 1996, de Heus 2004, Nyende 2004,Dodd 2005) (Level II). If beyond this time delivery or abortion has not occurred,options include surgical termination, expectant management, or anotherinduction attempt to be repeated in 24 hours after the first failed attempt (LevelIV). These options should be weighed in the context of the urgency in evacuationof the uterus and the patients desires for expediency. Variables that influencesuccess (defined as vaginal delivery within 24 hours) are: favourability of the

cervix (Bishop score >6), parity and gestational age (Hofmeyr 2003,Chittacharoen 2003, Fawole 2004).

Approximately 25% of women will have retained placental fragments; thisis a complication that is seen more frequently with second trimester inductions forIUFD than those in the third trimester (de Heus 2004, Fadalla 2004).


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Repeated dosingBefore administering a repeated dose for IUFD beyond 26 weeks, uterine

activity should be evaluated. If the patient has 2 or more contractions in 10minutes, the dose should not be repeated, because of the risk of uterinehyperstimulation. If the uterine contraction frequency diminishes, a repeat dose

may be given. If, however, the uterine contraction frequency persists or thepatient has demonstrated sufficient progress in cervical dilatation, intravenousoxytocin can be administered. We recommend that oxytocin should not beinitiated until four hours following administration of the last dose of misoprostol.

Maximum daily dosing should not exceed the following:o 13 to 17 weeks: 1600 mcg


o Beyond 26 weeks: 600 mcg

(Level IV, strong recommendation)

MonitoringClinical monitoring of the women should continue after delivery or

expulsion because of the risk of postpartum atony and/or placenta retention. Bothmay cause postpartum hemorrhage.

Etiologies for IUFD should be sought as appropriate for the institution(Silver, 2007). Similarly, bereavement and psychological support services shouldalso be provided to women before, during and after delivery of an IUFD.

RisksThere are no reports of maternal mortality and few reports of added

morbidities such as chorioamnionitis or excessive blood loss. In circumstanceswhere blood product transfusion was needed, many of the women hadunderlying malarial parasitemia which predisposed to this need (Bugalho,1994).(Level II)

EFFECTS AND SIDE EFFECTS:

The most commonly reported side effects include (Hofmeyr 2003, Neilson 2006):

Cramping: Uterine contractions are frequently painful. Pain

treatment such as NSAIDs and opioids may be used. Prophylactic

administration should also be considered. Gastrointestinal side effects as nausea, vomiting, and diarrhoea, up

to 35%

Pyrexia and shivering, up to 7%

The most serious complications associated with intravaginal misoprostol use forIUFD are premature separation of placenta, post-partum haemorrhaging, andrare events such as uterine rupture [particularly when used in women with prior


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Cesareans] and amniotic fluid embolism (Hofmeyr 2003). This requires closevigilance in observing women who are treated with misoprostol.

USE OF MISOPROSTOL IN THE COMMUNITY AND AT DIFFERENT HEALTHCARE LEVELS

Patients undergoing labor induction for second or third trimester IUFDshould deliver, whenever possible, in secondary or tertiary hospitals orcomprehensive emergency obstetric care (EmOC) qualified facilities based in thepossible complications (Level I-II, strong recommendation).

FREQUENTLY ASKED QUESTIONS

Is it safe to use misoprostol for patients with IUFD and previousCaesarean sections?

Answer: The risk for uterine rupture may increase in these cases, especially in

the third trimester. Therefore, it is advisable to use lower doses of misoprostolunder close clinical monitoring (Mariani-Neto 1987, Jain 1994, Nakintu 2001,Herabutya 2003, Dickinson 2005, Pongsatha 2003, Rouzi 2003, Daponte 2006).

(Level II)

When should oxytocin be added after misoprostol ?Answer: Oxytocin may be added only when the cervix is ripe, and regular uterinecontractions have not yet developed.. (Level II, strong recommendation)

How frequently will this treatment be effective?Answer: Most studies show a success rate of close to 100 per cent at 48 hours.

(Level I)

How should pain be managed for labor induction for IUFD?Answer:Pain should be treated in accordance with local standards. Thesetreatments may include non-steroidal anti-inflammatory agents, narcotics andepidural analgesia.

OPEN QUESTIONS AND RESEARCH SUGGESTIONS

1. Are higher misoprostol doses or shorter dosing intervals compared to the

suggested regimens appropriate for labor induction with second and thirdtrimester IUFD?

2. When available, what is the impact of pre-induction with mifepristone on thesuccess of induction for IUFD?

3. Is it safe to give misoprostol or continue to be given after a woman achievesadequate cervical ripening and/or enters early labor?

4. What is the safety and efficacy of orally or buccally administered misoprostolfor labor induction for IUFD?


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5. Could misoprostol could be used for retained placentas in second trimesterIUFD?


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Condensed guidelines

DEFINITIONIntrauterine fetal death: Intrauterine pregnancy beyond 12 weeks with a deadfetus, which has not been expelled.

CONTRAINDICATIONSContraindications are: Allergy to misoprostol and vaginal delivery

PRECAUTIONSA history of caesarean section(s) or uterine scarring increases the risk of uterinerupture. In these cases, lower doses should be used and doubling should notoccur.The risk for disseminated intravascular coagulation needs to be addressed.

REGIMENThe more advanced the pregnancy the lower the starting dose of vaginallyapplied misoprostol should be:

For IUFD from 13 to 26 weeks: Start with doses of:

200 mcg between 13 and 17 weeks' gestation.

100 mcg between 18 and 26 weeks' gestation.

For IUFD beyond 26 weeks

If the cervix is unripe, 25 to 50 mcg.

If the cervix is ripe, oxytocin is the treatment of choice. If not availableor not effective, the same regimen as for an unripe cervix should begiven. If oxytocin is necessary, begin after 4 hours followingadministration of the last dose of misoprostol.

Repeated treatment

For IUFD between 13 and 26 weeks, repeat the dose every 6 to 12 hours

for a total of four doses. If the first dose does not lead to effectivecontractions, it may be appropriate to double the subsequent doses:



For IUFD beyond 26 weeks, repeat the dose every 4 hours. If the first

dose does not lead to effective contractions, it may be appropriate todouble the subsequent dose to 50 or 100 mcg (depending on startingdose).

Maximum daily dosing in each of these cases should not exceed the

following:o 13 to 17 weeks: 800 mcg


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o Beyond 26 weeks: 600 mcg

If expulsion has not occurred in a timely manner, the same treatment

regimen can be repeated the following day.

COURSE OF TREATMENTConfirm fetal death with the available methods. Inform the patient of the clinicalscenario, its risks and proposed treatments. Check platelet count andcoagulation laboratory studies. Repeated doses must be avoided if the patienthas 2 or more contractions in 10 minutes.

EFFECT AND SIDE EFFECTS

Cramping: Available pain treatment, including NSAIDS and opioids,

should be given. Prophylactic treatment is also appropriate.

Gastrointestinal side effects as nausea, vomiting, and diarrhea

Pyrexia and shivering


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who chapter 8 intrauterine fetal death 27022007[final]

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