FETAL

DEATH
Nahida Chakhtoura and Uma M. Reddy
Maternal-Fetal Evidence Based Guidelines, 3rd Edi6on, 2017

Power point dibuat oleh

Judi Januadi Endjun

RSPAD Gatot Soebroto Puskesad FK UPN Veteran Jakarta
Departemen Obstetri dan Ginekologi
Subbagian Fetomaternal

2017
 KEY POINTS
Ultrasound examina>on should be
performed for conrma>on of fetal death.
Most informa6ve exams to nd the e>ology
of fetal death are autopsy; examina>on of
the placenta, cord, and membranes; and
chromosomal analysis.
Induc>on of labor in pa6ents with fetal death
is recommended unless pa6ent is already in
labor.
 KEY POINTS
For fetal death at about 14 to 28 weeks,
misoprostol (200400 mcg vaginally every 4
hours, 400 mcg orally every 4 hours, 200 mcg
buccal, or 600 mcg vaginally every 12 hours) is
the most cost-eec>ve method of delivery with
acceptable side eects.
AWer 28 weeks of gesta6on, drugs, such as
oxytocin and/or prostaglandins administered for
induc6on of labor, can be usually given according
to standard obstetric protocols (see Chapter 21 in
Obstetric Evidence Based Guidelines).
 DEFINITIONS
Fetal death is dened by the U.S. Na6onal Center for
Health Sta6s6cs (NCHS), a division of the Centers for
Disease Control and Preven6on, as
death prior to the complete expulsion or extrac5on from
the mother of a product of human concep5on,
irrespecBve of the duraBon of pregnancy and which is not
an induced terminaBon of pregnancy. The death is
indicated by the fact that aGer such expulsion or
extracBon, the fetus does not breathe or show any other
evidence of life such as beaBng of the heart, pulsaBon of
the umbilical cord, or denite movements of voluntary
muscles. Heartbeats are to be disBnguished from transient
cardiac contracBons; respiraBons are to be disBnguished
from eeBng respiratory eorts or gasps [1].
 DEFINITIONS
The WHO deni6on of fetal death does not exclude
spontaneous abor6on at <12 weeks, which has
dierent e6ologies and management than fetal death
occurring in the second or third trimester.
There is not complete uniformity even among U.S.
states regarding the birth weight and gesta6onal age
criteria for repor6ng fetal deaths.
However, NCHS has recommended the repor6ng of
fetal deaths at 20 weeks of gesta6on with known
gesta6onal age or weight 350 g if the gesta6onal age
is unknown [2].
350 g is the 50th percen6le for weight at 20 weeks of
gesta6on.
 DEFINITIONS
Fetal losses because of termina6ons of pregnancy for
lethal fetal anomalies and induc6ons of labor for
previable premature rupture of membranes are
excluded from these sta6s6cs and are classied
separately as termina6ons of pregnancy.
Embryonic death is dened as death occurring at 12
weeks.
Early fetal death is dened as death occurring at 13 to
19 6/7 weeks of gesta6on.
Intermediate fetal death is dened as death occurring
at 20 to 27 weeks of gesta6on.
Late fetal death is dened as death occurring at
greater than 28 weeks of gesta6on.
 DEFINITIONS
S>llbirth is the term preferred by parent groups
and therefore has been increasingly used by the
research community and by ACOG for fetal
deaths 20 weeks of gesta6on or weight >350 g
[3] and can be used as a synonym for fetal death.

Fetal demise (oWen abbreviated IUFD or

intrauterine fetal demise) is oWen also used
interchangeably with fetal death.
Unexplained fetal death is dened as death
before delivery with no iden6able cause aWer
complete evalua6on is performed.
 DIAGNOSIS
The diagnosis of fetal death should be
conrmed by ultrasound with absence of
heart movement.
 EPIDEMIOLOGY/INCIDENCE
An es6mated 3.2 million s6llbirths occur annually
worldwide; 98% of all s6llbirths occur in low- and
middle-income countries with two thirds of s6llbirths
occurring in Southeast Asia and Sub-Saharan Africa [4,5].
In the United States, in 2013, there were 23,595
reported fetal deaths at 20 weeks of gesta6on or
more, resul6ng in a fetal death rate of 5.96/1000 live
births plus fetal deaths [3].
Close to one half of these deaths occur in the third
trimester. U.S. fetal mortality rates have been stable
since 2006 with some minor uctua6ons [1,6].
 ASSOCIATION/RISK FACTORS/
POSSIBLE ETIOLOGIES
There are many maternal and fetal factors that have
been associated with fetal death (Table 55.1).
About 25% of fetal deaths are not associated with any
of these risks and are called unexplained.
Many classica6on schemes for assigning cause of
s6llbirth are currently used throughout the world.
There are at least 35 dierent classica6on systems
reported in the medical literature since 1954, and each
system was created with a specic purpose by the
inves6gators.
Table 55.1 Associa>ons/Risk Factors/Possible E>ologies of Fetal Death
Maternal Risk Factors Fetal Risk Factors
Chronic hypertension Congenital malforma>ons (15-20%)
Preeclampsia Chromosomal/gene>c abnormali>es (8-13%):
Diabetes Mellitus, thyroid disorders monosomy X, trisomy 21, trisomy 18, and
trisomy 13
Renal disease
Single gene disorders: hemoglobinopathies (e.g.
Systemic lupus erythematosus (SLE) alpha-thalassemia); metabolic diseases (e.g.
Autoimmune disease Smith-Lemil-Op6z syndrome)
An>phospholipid syndrome Missense muta6ons leading to long QT
Cholestasis of pregnancy syndrome
Alloimmuniza6on Glycogen storage diseases
Obesity Peroxisomal disorders amino acid disorders
Substance abuse (especially cocaine, Conned placental mosaicism (aneuploidy in
alcohol, coee: > 3 cups/day, etc) placenta with a euploid fetus)
Placental abrup6on, placenta, and vasa previa
Smoking
Placental pathology: Chronic villi6s, Masive
Viral infec6on: Parvovirus B19, CMV, chorionic intervillosi6s
Enteroviruses (e.g., coxsackie virus) Complica6ons of mul6fetal gesta6on (e.g. TTTS,
Echoviruses, HSV-1, HSV-2, HIV TRAP syndrome, and discordant growth)

Note: In bold, most common associa6ons.

Table 55.1 Associa>ons/Risk Factors/Possible E>ologies of Fetal Death
Maternal Risk Factors Fetal Risk Factors
Bacterial infec6ons: Umbilical cord complica6ons, fetomaternal
Listeria monocytogenes, Escheria hemorrhage
coli, Group B streptococci, Fetal growth restric6on

Ureaplasma urealy6cum,
Uteroplacental insuciency
Treponema pallidum
Intrauterine asphyxia
Parasi6c infec6ons:
Toxoplasma gondii Preterm labor or rupture of membranes

Uterine malforma>ons Posterm

Abdominal trauma

Note: In bold, most common associa6ons.

 ASSOCIATION/RISK FACTORS/
POSSIBLE ETIOLOGIES
The S6llbirth Collabora6ve Research Network
(SCRN) Ini6al Causes of Fetal Death was devised
for research purposes to provide a structured
system so that the deni6ons used to assign the
most likely cause of s6llbirth are uniform and
those reviewing the poten6al causes of s6llbirth
can communicate using a common language.
An important goal of this system was to use the
best available evidence and rigorous deni6ons
determined before case review when assigning a
cause of death [7].
 ASSOCIATION/RISK FACTORS/
POSSIBLE ETIOLOGIES
Fetal death rate is an important marker of quality of
health care.
Other factors associated with fetal death are advanced
maternal age, non-Hispanic black race, nulliparity or
mul6parity (>5), maternal medical disease, unmarried
status, low socioeconomic status, low educa6on,
mul6ple gesta6on, assisted reproduc6ve technology,
and past obstetric history (previous s6llbirth, preterm
delivery, postdates, or growth restric6on) [818].
Obesity, smoking, and drug and alcohol abuse are
common modiable risk factors for fetal death.
 ASSOCIATION/RISK FACTORS/
POSSIBLE ETIOLOGIES
Obesity, smoking, and drug and alcohol
abuse are common modiable risk factors for
fetal death.
Pes6cides, radia6on, and fer6lity drugs have
also been associated with fetal death [19].
In developing countries, the most common
causes of s6llbirths are complica6ons of labor
and infec6on.
 PREVENTION
Some of the risk factors listed in Table 55.1, in
par6cular obesity, smoking, and drug and alcohol
abuse, are modiable and should be avoided.
Basic emergency obstetric care, births in
adequate facili6es with op6on for safe cesarean
delivery (CD), improvement in nutri6on, and
preven6on and treatment of syphilis,
tuberculosis, and malaria are the most feasible
and cost-eec6ve interven6ons in developing
countries to decrease the incidence of s6llbirth
[20].
 PREVENTION
As the vast majority of fetal deaths occur in
developing countries, interven6ons should be
focused on preven6on in these sewngs and
include [21] the following:
Improving maternal nutriBonal status, such as
micronutrient supplementaBon
PericoncepBon folate forBcaBon [22]
InsecBcide-treated bed nets or intermiSent
preventaBve treatment for malaria
Syphilis detecBon and treatment
DetecBon and treatment of hypertensive disorders
 PREVENTION
As the vast majority of fetal deaths occur in
developing countries, interven6ons should be
focused on preven6on in these sewngs and
include [21] the following (conBnued):
DetecBon and management of diabetes in pregnancy
Smoking cessaBon
DetecBon and management of FGR
InducBon at 41 weeks (prevenBon of posSerm
pregnancy)
Skilled care at birth
Basic and comprehensive emergency obstetric care
 PREGNANCY MANAGEMENT
Counseling
Counseling should include review of possible
e6ologies (Table 55.1), workup (Table 55.2), and
delivery op6ons as well as possible complica6ons.
Grief counseling should be included in addi6on to the
op6on for referral to grieving help groups.
Understanding the cause of s6llbirth is important to
parents and management of future pregnancies.
However, obtaining consent for autopsies, surgical
inves6ga6ons, imaging and other inves6ga6ons is
dicult for both parents and health care providers.

 PREGNANCY MANAGEMENT
Counseling (conBnued)
Inves6ga6ng the best possible way to support
decision-making is important [23].
Review of risk of recurrence, preven6on of
recurrence, and best management for a future
pregnancy (Table 55.3) should be done
postpartum.
Workup
Table 552. Maternal and Fetal Inves>ga>on for Fetal
Death
PREDELIVERY
Amnio>c uid for cytogene>cs
Screen for coagulopathy (only if fetal death >4 wk from delivery)
CBC, an>body screen, urine drug screen
Kleihauer-Betke tes>ng or ow cytometry
Lupus an>coagulant, an>cardiolipin an>bodies (IgM, IgG) and an>-2-glycoprotein
an>bodies (IgM, IgG)
Parvovirus B19 >ters (IgM and IgG)a
Syphilis tes>ng (RPR or VDRL)
Thyroid-s>mula>ng hormone
Glucose screening (oral glucose tolerance test, hemoglobin A1c) (if glucose screening not
done in pregnancy)
Thrombophilia workup only to be considered in cases of
severe placental infarcts, fetal growth restric>on, or in the seeng of a personal history of
thrombosis (factor V Leiden muta>on; G20210A prothrombin gene muta>on; an>thrombin III)

POSTDELIVERY
Cord blood for cytogene6cs
Autopsy and placental examina>on
Protein C, protein S ac6vity (in selected cases as described above for other thrombophilia
workup)
MRI
Table 55.3 Management of Subsequent Pregnancy ager S>llbirth
PRECONCEPTION OR INITIAL PRENATAL VISITE
Detailed medical and obstetrical history
Evalua>on/workup of previous s>llbirth
Determina>on of recurrence risk
Discussion of increased risk of other obstetrical
complica>ons
Smoking cessa>on
Weight loss (back to normal BMI) in obese women
Gene>c counseling if family gene>c condi>on exists
Support and reassurance

FIRST TRIMESTER
Da6ng ultrasound by crownrump length ( rst trimester)
First-trimester screen-PAPP-A, hCG, and nuchal translucency
Diabetes screen
An6phospholipid an6bodies
Thrombophilia workup only if s6llbirth associated with severe placental infarcts, fetal
growth restric6on, or in the sewng of a personal history of thrombosis. Support and
reassurance

Source: Adapted from Horey D et al. Cochrane Database System Rev, 2, CD009932, 2013
Table 55.3 Management of Subsequent Pregnancy ager S>llbirth
SECOND TRIMESTER
Fetal anatomic survey at 18 to 20 wk
Quadruple screen-MSAFP, hCG, estriol, and inhibin-A
Uterine artery Doppler studies at 22 to 24 wk
Support and reassurance

THIRD TRIMESTER
Serial ultrasounds about every 4 wk to rule out fetal growth restric6on, star6ng at 28 wk
Fetal movement coun6ng star6ng at 28 wk
Antepartum fetal surveillance (e.g., nonstress tests or biophysical pro les) star6ng at 32 wk
or 1 to 2 wk earlier prior to gesta6onal age of previous s6llbirth if occurred prior to 32 wk
Support and reassurance

DELIVERY
Planned induc6on at 39 wk or before 39 wk if desired by the couple and lung maturity
documented by amniocentesis

Source: Adapted from Horey D et al. Cochrane Database System Rev, 2, CD009932, 2013
 PREGNANCY MANAGEMENT
Workup
Evalua6on of the e6ology of fetal death is
essen6al to counsel regarding recurrence risks,
facilitate the grieving process, and improve
understanding to facilitate therapeu6c measures
(Table 55.2) [3,24,25].
The evalua6on can be emo6onally dicult and
should be mul6disciplinary (obstetrician,
maternal-fetal specialist, pathologist, gene6cist,
radiologist, and neonatologist).
 PREGNANCY MANAGEMENT
Workup
Communica6on between all these members is
important. Sta interac6ng with the family should
refer to the s6llborn baby by name if one was
given. Parents should be informed about the
reasons for autopsy, procedures, and poten6al
cost.
The most important components of the
evalua>on of a s>llbirth are fetal autopsy;
examina>on of the placenta, cord, and
membranes; and karyotype analysis.
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following:
1. Review all relevant maternal, perinatal, family his-
tory, and risk factors to help iden6fy speci c possibili-
6es (Table 55.1). See specic guideline if a specic
risk factor is iden6ed as probable cause. In family
history, par6cular aten6on should be paid to
pregnancy losses, consanguinity, mental retarda6on,
diabetes, congenital anomalies with a three-
genera6on pedigree. All records should be reviewed
for any possible associa6on.
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable cause in
>60% of fetal deaths [26] and should include the
following (con6nued):
2. Before delivery, detailed ultrasound, fetal
echocardiogram, 3-D ultrasound, and whole-body X-rays
and/or MRI can be considered. These exams should be
recommended especially if a detailed autopsy will not be
available. Karyotypic analysis is not possible in 50% of
cases because of cell culture failure. To increase the yield
of cell culture, an amniocentesis (and/or CVS) should be
oered for karyotype [27] and fetal infec6on workup. Even
if 5% to 10% of cells from amnio6c uid of fetal deaths fail
to grow, this yield is much higher than that obtained from
postnatal study of karyotype [28].
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued) :
3. Before delivery, obtain consent for fetal autopsy. If
consent is not given for a full autopsy, ask the parents
to consider a limited autopsy, such as external
examina6on by pathologist/clinical gene6cist or
internal examina6on limited to brain and/or spinal
cord, chest organs, or abdominal organs as
appropriate, or an MRI [29].
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable cause in
>60% of fetal deaths [26] and should include the following
(con6nued) :
4. At delivery, examine baby and placenta carefully. General exam
immediately aWer delivery should include no6ng any
dysmorphology/congenital abnormali6es as well as obtaining
weight, length, and head circumference. Foot length may be
especially useful for earlier s6llbirths that may have a few weeks
lag between death and delivery to pinpoint gesta6onal age at
death. Photographs of the en6re body; frontal and pro le views
of the face, extremi6es, and palms; and close-up photo- graphs
of specic abnormali6es should be obtained [3]. The placenta
should be weighed and compared to the norms for gesta6onal
age. Clinical gene6cist evalua6on if available is oWen helpful.
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable cause in
>60% of fetal deaths [26] and should include the
following (con6nued) :
5. Prior to autopsy, karyotypic analyses should be per-
formed on all s>llbirths aWer parental consent is
obtained. Yield for abnormali6es is higher if the following
is present: fetus with growth restric6on, anomalies, or
hydrops or the parent is a balanced transloca6on carrier
or has a mosaic karyotype [3]. The most viable 6ssue for
cytogene>c and molecular gene>c studies is usually the
placenta (1 1 cm block) taken from below the cord
inser6on site on the unxed placenta or umbilical cord
closest to the placenta, followed by fetal car6lage
obtained from the costochondral junc6on or patella [3,30].

 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable cause in
>60% of fetal deaths [26] and should include the
following (con6nued) :
5. Placental >ssue can be sent for karyotype to check for
conned placental mosaicism. Skin surface should be
cleansed with betadine or hibiclens prior to obtaining
specimen. Tissue should be placed in Hanks solu6on (pink)
or normal saline if Hanks solu6on is not available, not in
formalin. Cytogene6c form should be completed with
per6nent details. Atempts at cell culture, however, fail in
half of the cases. If culture is unsuccessful, uorescent in
situ hybridiza>on to detect most common aneuploidies or

 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
5. compara>ve genomic hybridiza>on (cGH), which
detects small dele6ons or duplica6ons, and termed
copy number changes not detectable by karyotype
may be useful since both technologies do not require
live cells [31]. Tes6ng for rarer causes of s6ll- birth
such as single gene disorders or muta6ons in Long QT
genes should be guided by clinical suspicion or family
history [32].
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
6. Autopsy is the most useful test in iden6fying the
cause of fetal death. Not only are gross birth defects
and morphologic abnormali6es iden6ed, but subtle
ndings of the autopsy may conrm infec6on,
anemia, hypoxia, and metabolic abnormali6es as the
cause of death. Autopsy reduces the number of
unexplained fetal deaths by at least 10% [33].

 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
6. Autopsy ndings altered counseling and recurrence
risks autopsy in 26% of all cases at one ins6tu6on [34].
The addi6on of autopsy to clinical and laboratory
data and placental examina6on resulted in improved
iden6ca6on of probable cause of death to 74% in a
cohort study at a ter6ary care center [35].
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
6. Autopsy should include X-rays of the fetus and
photographs and follow College of American
Pathologists guidelines (htp://www.cap.org). Whole-
body X-ray with anteriorposterior and lateral views
may reveal an unrecognized skeletal abnormality or
further dene an already visible abnormality.
Es6ma6on of the interval between intrauterine death
and delivery should be performed.
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
6. Clinical informa6on, all records including ultrasound
reports regarding the case, and any specic requests,
should be made available to the pathologist. It is
suggested for the obstetrician to call the pathology
resident/alending assigned to autopsy for
discussion. A perinatal pathologist with experience in
fetal death cases should perform the autopsy.
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
6. Examina6on by a physician experienced in gene6cs
and dysmorphology may increase the yield of
autopsy. If autopsy is declined, it is important to
consider a head- sparing autopsy or at least MRI of
the s6llborn child [36]. If a complete autopsy is not
feasible, minimal invasive autopsy, which includes
postnatal MRI, blood sampling from the dead fetus at
autopsy, clinical history review, and external
evalua6on can be performed [37].
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
6. Examina6on Ultrasound of the brain may also be
considered for conrma6on or rening the
diagnosis of gene6c syndromes and
chromosomal abnormali6es in addi6on to
autopsy [38].

 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
7. Send placenta, membranes, and umbilical cord for
gross and microscopic pathologic examina>on.
Condi6ons causing or contribu6ng to s6llbirth may be
diagnosed, such as abrup6on, placental infarcts,
umbilical cord thrombosis, velamentous cord
inser6on, and vasa previa. Placental evalua6on can
also yield important informa6on regarding infec6on,
gene6c abnormali6es, anemia, and thrombophilia.
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
7. Umbilical cord knots and tangling should be noted
but interpreted carefully as cord entanglement
occurs in 30% of normal pregnancies [3,39].
Examina6on of the placenta vasculature and
membranes is par6cularly useful in mul6fetal
gesta6ons by establishing chorionicity and vascular
anastomoses.
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
8. If autopsy, placental pathology, or history is
sugges6ve of an infec6ous e6ology, maternal or
neonatal serology, special 6ssue stains, and/or
tes6ng for bacterial or viral nucleic acids may be
undertaken. If clinical or histologic evidence is
lacking, then rou6ne tes6ng for infec6on is of
ques6onable benet.
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
9. Maternal labs [3] (Table 55.2):
a. KleihauerBetke tes6ng or ow cytometry are sent to
evaluate for fetalmaternal hemorrhage (prior to delivery is
op6mal).
b. Lupus an6coagulant, an6cardiolipin an6bodies (IgM, IgG),
and an6- -glycoprotein an6bodies (IgM, IgG) can be sent to
2

test for an6phospholipid syndrome.

 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
9. Maternal labs [3] (Table 55.2) (conBnued):
b. Presence of lupus an6coagulant or an6cardiolipin an6-
bodies of moderate to high 6ter (>40 immunoglobulin M
(IgM) binding/immunoglobulin G (IgG) binding or >99th
percen6le) or an6-2-glycoprotein an6body 6ter (>99th
percen6le) are all considered posi6ve but should be con
rmed with repeat tes6ng 12 weeks later [40] (see also
Chapter 26).
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
9. Maternal labs [3] (Table 55.2) (con6nued):
c. Parvovirus B19 6ters (IgM and IgG) can be considered,
especially in cases in which there is suspicion for this
infec6on, such as those with fetal hydrops or fetal anemia
[41]. CMV, toxoplasmosis, and other viruses and/ or bacteria

are not suggested for workup, unless clinical history or

other factors (pathology ndings) point to these infec6ons.
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
9. Maternal labs [3] (Table 55.2) (con6nued):
d. Syphilis tes6ng can be sent with RPR or VDRL.

e. Glucose screening (oral glucose tolerance test, hemoglobin
A1c) (if glucose screening not done in pregnancy).

 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
9. Maternal labs [3] (Table 55.2) (con6nued):
f. Thrombophilia workup should be sent only in cases of
severe placental pathology, fetal growth restric6on, or in
the sewng of a personal history or history in a rst- degree
rela6ve (e.g., parent or sibling) of thrombosis (factor V
Leiden muta6on; G20210A prothrombin gene muta6on;
deciencies of an6thrombin III, protein C, protein S) (see
Chapter 27). Rou6ne tes6ng is controversial and may lead
to unnecessary interven6ons [3].
 PREGNANCY MANAGEMENT
Workup
A complete evalua6on [3] iden6es a probable
cause in >60% of fetal deaths [26] and should
include the following (con6nued):
10.Consider any other workup, depending on risk factor
iden6ed in Table 55.1. For fetal demise before 20
weeks, consider individualized workup and refer to
chapter on pregnancy loss (Chapter 15 in Obstetric
Evidence Based Guidelines).

 DELIVERY/ANESTHESIA
Once diagnosis is conrmed and counseling
and workup ini6ated, op6ons for delivery
should be discussed.
Op>ons include expectant management,
induc>on, or dila>on and evacua>on (D&E).
Expectant Management
Dilata6on and Evacua6on
Induc6on
 DELIVERY/ANESTHESIA
Expectant Management
Between 80% and 90% of women with fetal death
will spontaneously enter labor within two weeks of
fetal demise [42].
Dura6on of labor is shorter in pa6ents with
spontaneous labor [43].
However, endomyometri>s rate is higher in the
spontaneous labor group (6% vs. 1%) compared to
induc6on.
There is no dierence in the frequency of postpartum
hemorrhage, retained placenta, or need for blood
transfusion.
 DELIVERY/ANESTHESIA
Expectant Management
Reten6on of a dead fetus can cause chronic consump6ve
coagulopathy because of gradual release of
thromboplas6n from the placenta into the maternal
circula6on [30].
This usually occurs aWer four weeks but may occur earlier.
Coagula>on abnormali>es occur in about 3% to 4% of
pa6ents with uncomplicated fetal deaths over the next
four to eight weeks, and this number rises in the presence
of abrup6on or uterine perfora6on [30].
Another disadvantage of expectant management is a long
interval between fetal death and spontaneous labor,
limi6ng the amount of informa6on that can be obtained
about the cause of death from a postmortem examina6on
or autopsy of the baby.
 DELIVERY/ANESTHESIA
Expectant Management
Moreover, women with fetal death nd it dicult
psychologically to con6nue a pregnancy with a known
fetal death [44].
In pa6ents op6ng for spontaneous labor (especially
with greater than four-week interval between fetal
death and >me of delivery), a screen for
coagulopathy (brinogen level, platelet count,
prothrombin 6me, and ac6vated par6al
thromboplas6n measurement) should be obtained
prior to administra6on of neuraxial anesthesia as well
as other invasive procedures [30].
 DELIVERY/ANESTHESIA
Dilata>on and Evacua>on
Comparing complica6on rates of pa6ents who
undergo D&E or medical induc6on between 14
and 24 weeks of gesta>on, D&E is a safe method
in this 6me frame, especially if done by
experienced operators under con>nuous
ultrasound guidance [45].
Surgical termina6on of pregnancy between 14
and 24 weeks of gesta6on has a lower overall rate
of complica6ons (4%) as compared to 29% in
women undergoing labor induc6on [45].
 DELIVERY/ANESTHESIA
Dilata>on and Evacua>on
Pa6ents undergoing D&E are less likely to have
failure of the ini6al method for delivery and
retained products of concep6on.
However, both groups are similar in the need for
blood transfusion, infec6on, cervical lacera6on,
maternal organ damage, or hospital readmission.
Placement of laminaria is associated with a lower
risk of complica6ons from D&E, and misoprostol
is associated with a lower complica6on rate in
women undergoing medical termina6on [45].
 DELIVERY/ANESTHESIA
Dilata>on and Evacua>on
A Cochrane review [46] concluded that D&E is
superior to ins6lla6on of prostaglandin F2a and
may be favored over mifepristone and
misoprostol although larger randomized studies
are needed.
Using decision analysis, a cost-eec6veness
analysis concluded that D&E is less expensive and
more eec6ve than misoprostol induc6on of labor
for second-trimester pregnancy termina6on [47].
 DELIVERY/ANESTHESIA
Dilata>on and Evacua>on
Studies do not show an increased rate of
complica6ons in subsequent pregnancies aWer D&E
although data are limited [48,49].
Both methods for delivery are considered reasonably
safe.
Thus, mode of delivery should usually be based on
the pa>ents wishes.
However, pa6ents should be counseled that ecacy
of autopsy is very limited with D&E [3].
In addi6on, the availability of D&E may be limited by
provider experience or gesta>onal age.
 DELIVERY/ANESTHESIA
Induc>on
Induc6on of labor in women with fetal death is
usually recommended unless the pa6ent is
already in labor given the problems men6oned
with expectant management.
Induc6on of labor is typically ini>ated soon ager
diagnosis of fetal death.
Most of the data for management of fetal death is
from randomized trials of second-trimester
pregnancy termina6on.
 DELIVERY/ANESTHESIA
Induc>on
Up to 28 Weeks
Op6ons for induc6on of labor for fetal death at about
16 to 28 weeks include misoprostol (prostaglandin E1,
PGE1), prostaglandins E2 (PGE2), high-dose oxytocin,
and hypertonic saline.
Misoprostol (preferred) and high-dose oxytocin are
the two modali>es with the best safety and
eec>veness evidence.
Available evidence from randomized trials do support
the use of vaginal misoprostol as a medical treatment
to terminate nonviable pregnancies before 24 weeks of
gesta6on [50,51].
 DELIVERY/ANESTHESIA
Induc>on
Up to 28 Weeks
On the basis of the limited data, the use of misoprostol
between 24 to 28 weeks of gesta6on also appears to
be safe and eec6ve [50].
Therefore, for gesta>ons less than 28 weeks,
misoprostol is the most ecient method of induc>on
regardless of Bishop score although high-dose oxytocin
infusion is an acceptable alterna6ve [3].
Typical dosages for misoprostol use are 200 to 400 mcg
vaginally, orally, or 200 mcg buccal every 4 to 12 hours
[3].
 DELIVERY/ANESTHESIA
Induc>on
Up to 28 Weeks
Examples of regimens for misoprostol dosing are
200 mcg vaginally every 4 hours, 400 mcg orally
every 4 hours, 200 mcg buccal, or 600 mcg
vaginally every 12 hours.
These result in successful expulsion (mostly within
24 hours) in 80% to 100% of cases [3,52 54].
 DELIVERY/ANESTHESIA
Induc>on
Up to 28 Weeks
Misoprostol 400 mcg given orally every 4 hours is
more eec>ve than misoprostol 200 mcg given
vaginally every 12 hours for the induc>on of second-
and third-trimester pregnancy with intrauterine fetal
death within 24 hours but is associated with more
gastrointes6nal side eects [52,55].
Misoprostol 600 mcg administered vaginally at 12-hour
intervals is associated with fewer adverse eects and is
as eec6ve as dosing at 6-hour intervals [53].
 DELIVERY/ANESTHESIA
Induc>on
Up to 28 Weeks
High-dose oxytocin (200 units in 500 mL saline at 50
mL/hour) also may be used for induc>on of labor
remote from term [56].
The mother should be observed for signs of water
intoxica>on, and maternal electrolyte concentra>ons
should be monitored at least every 24 hours.
Nausea and malaise are the earliest ndings of
hyponatremia and may be seen when the plasma
sodium concentra6on falls below 125 to 130 mEq/L.
 DELIVERY/ANESTHESIA
Induc>on
Up to 28 Weeks
This may be followed by headache, lethargy, obtunda6on,
and eventually seizures, coma, and respiratory arrest.
Misoprostol 50 g with dose doubled every 6 hours un6l
eec6ve contrac6ons is associated with a success rate
within 48 hours of induc6on of 100% compared to 96.7% to
oxytocin infusion 6trated on the basis of pa6ent response
with mean induc>on to delivery >me signicantly longer
(almost double) in the oxytocin group compared with the
misoprostol group (23.3 vs. 12.4 hours).
Misoprostol is also cheaper (1/10th the price of oxytocin)
[57].
 DELIVERY/ANESTHESIA
Induc>on
Up to 28 Weeks
Historically, PGE2 suppositories with a dose of 20 mg
inserted vaginally every four hours were also u6lized
for labor induc6on before 28 weeks.
Pretreatment with acetaminophen, compazine, and
diphenoxylate is useful to minimize fever, nausea,
vomi6ng, and diarrhea, which invariably occur.
The PGE2 dose should be reduced to 5 to 10 mg if used
at a more advanced gesta6on (o-label use) as uterine
sensi6vity and the risk of uterine rupture increase with
gesta6onal age [58].
 DELIVERY/ANESTHESIA
Induc>on
Up to 28 Weeks
High-dose PGE2 suppositories are contraindicated >28
weeks gesta6on [59].
Misoprostol is more ecacious and at least as safe and
cheaper than PGE2, and so the use of PGE2 for
induc6on of fetal death before 28 weeks is not
recommended and of mostly historic importance only.
The ecacy and tolerance of mifepristone (RU 486), a
progesterone antagonist, was inves6gated in a double-
blind controlled mul6center study involving 94 pa6ents
with an intrauterine fetal death [60].
 DELIVERY/ANESTHESIA
Induc>on
Up to 28 Weeks
Success of treatment was dened as the occurrence of
fetal expulsion within 72 hours aWer the rst drug
intake.
Mifepristone treatment (600 mg/day for two days) was
considered to be eec6ve in 29 of 46 pa6ents (63%).
There were only eight successes in 48 pa6ents (17.4%)
in the placebo group (p = .001).
Tolerance was good in the mifepristone group. In the
placebo group, disseminated intravascular coagula6on
occurred in one woman for whom the inves6gator
waited several weeks for spontaneous expulsion.
 DELIVERY/ANESTHESIA
Induc>on
Up to 28 Weeks
Another RCT compared high-concentra6on
oxytocin to misoprostol given 36 hours aWer ini6al
mifepristone 200 mg in second trimester abor6on
for either IUFD or voluntary termina6on.
The mifepristoneoxytocin regimen had longer
6me un6l expulsion but fewer side eects [61].
 DELIVERY/ANESTHESIA
Induc>on
Up to 28 Weeks
Mifepristone is of interest in the management of
intrauterine fetal death with more studies needed
to compare the above methods, in par>cular
misoprostol with mifepristone.
To date, there are no studies evalua6ng laminaria
for ripening of the cervix in conjunc6on with other
methods of induc6on for cases of fetal death.
 DELIVERY/ANESTHESIA
Induc>on
AGer 28 Weeks
AWer 28 weeks of gesta6on, drugs such as
oxytocin and/or prostaglandins administered for
induc>on of labor can be given according to
standard obstetric protocols [3] (see Chapter 21 in
Obstetric Evidence Based Guidelines).
Cesarean delivery for s6llbirth is reserved for
unusual circumstances (maternal indica6ons)
because it is associated with maternal morbidity
without fetal benet [3].
 DELIVERY/ANESTHESIA
Induc>on
Women with Prior Uterine Scar
Women with a prior uterine scar represent a special
group and treatment should be individualized. For
women with a previous low transverse incision and a
uterus less than 28 weeks size, the usual protocols for
misoprostol induc>on at less than 28 weeks may be
used [3,50].
Several studies have evaluated the use of misoprostol
at a dosage of 400 mcg every six hours in women with a
s6llbirth up to 28 weeks of gesta6on and a prior
uterine scar [62,63].
 DELIVERY/ANESTHESIA
Induc>on
Women with Prior Uterine Scar
There does not appear to be an increase in
complica6ons in those women.
The risk of uterine rupture is about 0.4% with one
prior low transverse CD, up to 9% with 2 prior CD,
and up to 50% with prior ver6cal CD [64].
Further research is required to assess eec6veness
and safety, op6mal route of administra6on, and
dose [50].
 DELIVERY/ANESTHESIA
Induc>on
Women with Prior Uterine Scar
For women with a previous low transverse
incision, ager 28 weeks of gesta>on, oxytocin
protocols may be u>lized and cervical ripening
with Foley bulb may be considered [3,50].
Pa6ents may elect for a repeat CD in the sewng of
a s6llbirth, but the risks and benets should be
discussed with the pa6ent.
 DELIVERY/ANESTHESIA
Induc>on
Women with Prior Uterine Scar
Ideally, a cesarean should be avoided.
Therefore, on the basis of limited data in pa6ents
with a prior low transverse CD, trial of labor
remains a favorable op6on [3,50].
There are limited data for pa6ents with a prior
classical uterine incision or prior myomectomy;
therefore, the delivery plan should be
individualized [3,50].
 POSTPARTUM
Prior to discharge, the family needs to be
counseled that results of all inves6ga6ons
may take two or three months for comple6on
and that despite extensive evalua6on a cause
of death may not be found.
Pa6ents should be oered the opportunity to
see and hold their infant and be oered
keepsake items such as photos, hand/
footprints, or special blankets or clothing.
 POSTPARTUM
Grief counseling should be ini6ated prior to
discharge from hospital.
Referral to a bereavement counselor, religious
leader, peer support group, or mental health
professional is advisable for management of
grief and depression.
Fetal death causes very much grief also in
the majority of obstetricians, who can
experience self-doubt, depression, and self-
blame in rela6on to their pa6ents loss [65].
 PREVENTION OF RECURRENCE AND
MANAGEMENT IN A FUTURE PREGNANCY
A special outpa>ent visit should be set up to
review the results of the complete workup and
discuss possible e6ology and future management
(Table 55.3).
If a par6cular medical problem is iden6 ed in the
mother, it should be addressed prior to next
concep6on (see specic guidelines).
For example, 6ght control of blood glucose prior
to concep6on can substan6ally reduce the risk of
congenital anomalies in the fetus.
Preconcep6on counseling is helpful if congenital
anomalies or gene6c abnormali6es are found.
 PREVENTION OF RECURRENCE AND
MANAGEMENT IN A FUTURE PREGNANCY
In the future, compara6ve genomic
hybridiza6on, FISH, and other novel gene6c
techniques will provide beter ways to workup
the myriad gene6c causes of fetal death.
A woman with a prior fetal loss and either
factor V or prothrombin heterozygocity or
protein S deciency might benet from
enoxaparin 40 mg SQ daily star6ng at eight
weeks [53].
 PREVENTION OF RECURRENCE AND
MANAGEMENT IN A FUTURE PREGNANCY
Compared with low-dose aspirin, in women who
had had a previous fetal loss aWer the 10th week
and had a thrombophilic defect (heterozygous
factor V Leiden, prothrombin G20210, or protein
S deciency), enoxaparin 40 mg daily treatment
is associated with a tenfold increased live birth
rate as compared with low-dose aspirin in only
one trial [66].
In some cases, such as cord occlusion, the pa6ent
can be assured that recurrence is unlikely [39,67].
 PREVENTION OF RECURRENCE AND
MANAGEMENT IN A FUTURE PREGNANCY
Overall, there is an increased incidence of
pregnancy complica6ons, such as
sBllbirth (2.5- to 10-fold increase depending on the
study) [17,68],
preterm birth (OR 2.8, 95% CI 1.94.2),
preeclampsia (OR 3.1, 95% CI 1.75.7), and
placental abrupBon (OR 9.4, 95% CI 4.519.7) [80]
in subsequent pregnancies [69].
Most pa6ents nd increased fetal surveillance
with the next pregnancy reassuring.
 PREVENTION OF RECURRENCE AND
MANAGEMENT IN A FUTURE PREGNANCY
Fetal growth ultrasounds and kick counts
star>ng at 28 weeks and antepartum
surveillance star>ng at 32 weeks may be
implemented [3].
In a woman with a prior IUFD, planned induc6on
can be discussed with the pa6ent in terms of
risks and benets [3].
If any of the surveillance demonstrates no
maternal or fetal issues complica6ng the
pregnancy, considera6on for 38 0/739 6/7 week
induc6on should be considered [70].
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