Original Article

Can We Prevent Stillbirth?

Yuval Fouks, MD1 Roi Tschernichovsky, MD1 Ariel Greenberg, MD2 Stella Bak, MD2
Noa Brzezinski Sinai, MD3 Shiri Shinar, MD1

1 Department of Obstetrics and Gynecology, Sourasky Medical Center,
Lis Maternity Hospital, Tel Aviv University, Tel Aviv, Israel
2 Division of Pathology, Sourasky Medical Center, Tel Aviv University,
Tel Aviv, Israel
3 Helen Schneider Hospital for Women, Rabin Medical Center, Tel Aviv
University, Petach Tikva, Israel
Address for correspondence Yuval Fouks, MD, Department of
Obstetrics and Gynecology, Sourasky Medical Center, Lis Maternity
Hospital, Sackler School of Medicine, Tel Aviv University, 6 Weizmann
Street, Tel Aviv 64239, Israel (e-mail: fouksi@gmail.com).

Am J Perinatol

Abstract Objective To identify the frequency of potentially preventable causes of stillbirth in a

large heterogeneous population.
Study Design This is a retrospective study of all stillbirth cases between January 2011
and December 2016 at a single tertiary medical center. Deliveries resulting from a

Downloaded by: Boston University. Copyrighted material.

nonviable fetus prior to 24 weeks of gestation, intrapartum fetal death, and incomplete
stillbirth workup were excluded. Potentially preventable stillbirth was defined as that of
a nonanomalous fetus that most likely resulted from one or more of the following: (1)
placental-mediated complications, (2) postterm pregnancy, (3) monochorionicity-
associated complications, (4) cholestasis of pregnancy, (5) preventable or treatable
infections, and (6) isoimmunization.
Results During the study period, 312 stillbirths were identified, 228 of which met the
inclusion criteria. Of the 110 cases with a recognized cause, 47 (20.6%) were potentially
preventable. The most common causes were placental-mediated complications and
Keywords preventable or treatable infections, accounting for 75 and 9% of all potentially
► stillbirth preventable causes, respectively. There were no recognizable maternal risk factors
► intrauterine for potentially preventable stillbirth.
► fetal death Conclusion One-fifth of all causes of stillbirth are potentially preventable. Due to the
► stillbirth prevention significant contribution of placental-mediated complications to preventable stillbirth,
► fetal pathology close sonographic surveillance and timely delivery may decrease risk substantially.

Stillbirth is a major contributor to perinatal mortality in both
developing and developed countries.1 The incidence of this
devastating obstetrical complication, with its global rate of 18.4
to 1,000 births,2 has changed little in the past decade,3 despite
its reduction being identified repeatedly by the U.S. Depart-
ment of Health and Human Services as an important goal.1,4
Risk factors associated with stillbirth have long been iden-
tified and include advanced gestational age, advanced maternal
age, smoking, low socioeconomic status, maternal overweight
or obesity,5 primiparity, and limited prenatal care.6 A recent
study investigating stillbirth in a large diverse U.S. cohort found
that 22.3% of the cases were potentially preventable with
adequate prenatal care.7 Nonetheless, in a survey of U.S. obste-
trician–gynecologists, 30% of the surveyed population was
unaware of the stillbirth risk factors and performed only partial
and inconsistent assessment of potential stillbirth causes.8
Due to the significant contribution of preventable still-
birth to all stillbirth causes, on the one hand, but lacking
awareness of care providers to these causes on the other
hand, we aimed to identify the frequency of preventable
causes of stillbirth in a large heterogeneous population and
elucidate their associated risk factors.

received Copyright © by Thieme Medical DOI https://doi.org/

October 7, 2018 Publishers, Inc., 333 Seventh Avenue, 10.1055/s-0039-1683960.
accepted after revision New York, NY 10001, USA. ISSN 0735-1631.
February 13, 2019 Tel: +1(212) 584-4662.
Preventable Stillbirths Fouks et al.
Methods
Subjects
All cases of stillbirth occurring between January 2011 and
December 2016 at a university affiliated tertiary medical
center were collected and extensively reviewed by two
independent maternal–fetal medicine specialists. This study
was conducted in a large medical center that serves a
heterogeneous population with diverse ethnic, socioeco-
nomic, and medical backgrounds. Stillbirth was defined as
delivery of a nonviable neonate at or beyond 20 completed
weeks of gestation.9 Gestational age was determined accord-
ing to last menstrual period and ultrasonography during the
first trimester, or second trimester if there were no preced-
ing dating scans. Exclusion criteria included deliveries result-
ing from pregnancy termination of a live fetus, spontaneous
preterm previable delivery of a fetus prior to 24 weeks of
gestation, and incomplete stillbirth workup (as described
later). Cases of intrapartum fetal death were excluded as well
since our aim was to elucidate potentially modifiable causes
associated with prenatal follow-up and not those associated
with intrapartum management, the latter being highly
dependent on the subjective interpretation of fetal heart
tracings.
Stillbirth Evaluation
A comprehensive workup of each case of stillbirth was
performed. Each patient underwent questioning regarding
family history, social background, personal, medical and
obstetrical history, complications in pregnancy, smoking,
and drug or alcohol use.
At the time of diagnosis, a complete blood count, Klein-
hauer–Betke test, HgbA1c, and urine toxicology were
obtained. In addition, maternal serologies for rubella, hepa-
titis B and C, HIV, varicella zoster, herpes simplex, syphilis,
cytomegalovirus, parvovirus B19, and toxoplasma gondii
were obtained. Antiphospholipid antibody screening was
performed after discharge in an outpatient setting and was
therefore not attainable.
Immediately, postpartum placental swabs for bacterial
and viral cultures were taken from the fetal and the maternal
placental poles. Neonatal swabs from the nasopharynx and
anus were obtained as well. In cases in which the parents
opted for an autopsy, the fetus and placenta were analyzed by
two fetal pathology experts. Microscopic placental analysis
was performed in accordance with practice guidelines for
placental evaluation.10,11
Preventable Stillbirth Definition
As there is no uniform definition for a preventable cause of
stillbirth, we defined a potentially preventable cause as that
for which appropriate medical management could have
altered the fetal outcome, resulting in a live birth. More
specifically, in these cases, the probable cause of death may
have been prevented by enhanced prenatal care including
more frequent ultrasonographic assessments and timely
labor induction. According to this definition, and relying
on previous categorization systems of American College of
American Journal of Perinatology
Obstetricians and Gynecologists and the initial causes of fetal
death criteria set by the Stillbirth Collaborative Research
Network12 preventable and unpreventable stillbirth etiolo-
gies were defined (►Table 1).
The potentially preventable stillbirth causes were
divided into six categories. First, placental-mediated com-
plications were considered a potentially preventable cause.
Prenatal surveillance is meant to diagnose these conditions,
and timing of delivery is determined accordingly, so that
maximal fetal maturation is gained but the risk of stillbirth
is mitigated.7,12 Second, near postterm pregnancy, which
we defined as a gestational age beyond 41 þ 3 weeks,13,14 is
associated with a rise in the incidence of stillbirth, and
therefore, regarded as preventable by timely delivery. Our
institutional guidelines recommend induction of labor at
41 þ 3 weeks, so cases of true postterm (>42 weeks)
stillbirth were rare. In all cases attributed to gestational
age, pathological findings were indicative of recent fetal
death. Third, stillbirth due to monochorionic complications
was considered avertable. The incidence of stillbirth rises
Downloaded by: Boston University. Copyrighted material.
with multiple pregnancies, primarily monochorionic gesta-
tions. Enhanced targeted sonographic surveillance is aimed
at detecting complications associated with monochorioni-
city, such as twin-to-twin transfusion syndrome and twin
anemia polycythemia sequence. Timely intervention can
result in improved outcomes and stillbirth prevention of
one or both twins.15,16 Fourth, we regarded isoimmuniza-
tion as a preventable cause, since routine prenatal care
detects the presence of hemolytic antibodies and is geared
at detecting fetal anemia. Delivery or blood transfusion can
be offered in these cases, thus preventing the sequelae of
stillbirth. Fifth, we classified intrahepatic cholestasis of
pregnancy as a preventable cause, as it is a well-recognized
complication that may lead to acute fetal distress and
associated stillbirth from 37 weeks of gestation onward.
Detection and timely term delivery can prevent this devas-
tating outcome.17,18 Finally, some infectious etiologies of
fetal death were considered potentially preventable. These
included stillbirth within 3 days of amniocentesis, with
clinical and placental findings highly suggestive of infec-
tion, and chorioamionitis likely due to maternal serocon-
version to parvovirus or syphilis in pregnancy. Proper
abdominal prepping in the former and detection and treat-
ment in the latter can potentially prevent resultant fetal
death.19,20
Unexplained stillbirth was defined as those cases where
extensive workup did not yield a probable cause. For the
purpose of the analysis, these cases were grouped together
with unpreventable stillbirth causes and compared with
potentially preventable ones.
The study was approved by our Institutional Review Board.
Statistical Analysis
Descriptive statistics for the characterization of preventable
versus unpreventable and unexplained causes are presented
as mean (standard deviation), median (interquartile ranges),
and n (%) where appropriate. A comparison between these
groups was performed using a chi-square test or a Fisher’s
 Table 1 Abnormal placental findings and related autopsy findings in cases of stillbirth

Patient GA at Amsterdam criteria SCRN Preventable/ Umbilical Overt Overt Placental findings Positive autopsy
stillbirth classification unpreventable cord findings acute placental findings
abruption inflammation
Patient 1 40 Maternal vascular 2H3 Preventable No No No Retroplacental hematoma Pulmonary, intestinal
malperfusion (chronic) and brain hemorrhage
Patient 2 34 Fetal and maternal vascular 2H3 Preventable No No No Multiple infarction, mild hyperpla-
malperfusion sia, and congestion of membranous
chorion
Patient 3 27 Intrauterine infection 2H3 Preventable No No Yes Multiple hematomas, infarctions
(chronic)
Patient 4 22 Intrauterine infection 2H3 Preventable Cord vasculitis No Yes Subchorionic and retroplacental Intrauterine pneumonia
hematoma
Patient 5 39 Fetal vascular malperfusion 2L4 Preventable Extensive umbilical cord No No Extensive infarction of umbilical Hypoxic changes in
hematoma cord, multiple small placental myocardium
infarcts, mild basal plate
inflammation
Patient 6 24 Intrauterine infection þ 2L4 Preventable Stasis in one umbilical artery. No Yes Chorionitis IUGR
fetal vascular malperfusion Thrombosis cannot be Basal plate inflammation
(suspected) excluded
Patient 7 34 Fetal and maternal vascular 2H3 Preventable No No No Stasis of umbilical cord Brain hypoxia and
malperfusion Retrodecidual hematoma edema
Patient 8 38 Maternal vascular 7A3 Preventable No No No Multiple infarctions, increased Cerebellar and intestinal
malperfusion number of syncytial knots, hypo/ hemorrhage, stasis of
irregular perfusion, stasis of blood blood vessels in heart
vessels
Patient 9 37 Fetal and maternal vascular 2H3 Preventable Hypercoiled umbilical cord No No Subchorionic hemorrhage,
malperfusion retrodecidual (chronic) hematoma,
peri- and intravillous fibrohyaline
changes
Patient 10 38 Fetal and maternal vascular 6F3 Preventable Marginal insertion No No Dichorionic diamniotic twins,
malperfusion hypo/irregular perfusion
Patient 11 31 Fetal and maternal vascular 2L4 Preventable Stasis in umbilical artery. No Yes DCDA twins with multiple infarcts, IUGR
malperfusion (mostly) Thrombosis cannot be extensive fibrous hyaline deposi-
excluded tion, increased number of syncytial
knots
One sac with early chorionitis and
marked stasis in umbilical cord
Signs of severe hypo/irregular
perfusion
Patient 12 30 Fetal vascular malperfusion 2L4 Preventable Very large subchorionic and No Yes Disrupted placenta, very large IUGR
Preventable Stillbirths

intraplacental hematoma subchorionic and intraplacental

involving umbilical cord hematoma at umbilical cord
insertion insertion, surrounded by fibrohya-
line and inflamed placental tissue,
hypoperfusion, mild early acute
membranous chorionitis
(Continued)
Fouks et al.

American Journal of Perinatology

Downloaded by: Boston University. Copyrighted material.
 Table 1 (Continued)

Patient GA at Amsterdam criteria SCRN Preventable/ Umbilical Overt Overt Placental findings Positive autopsy
stillbirth classification unpreventable cord findings acute placental findings
abruption inflammation
Patient 13 24 Fetal vascular malperfusion 2L4 Preventable Marginal insertion No Yes Areas of fibrohyalinosis and mild IUGR, cerebellar
(structural origin) chronic inflammatory infiltrate, hemorrhage, delayed
mild irregular hydrops bone ossification
Patient 14 20 Maternal vascular 2L4 Preventable No No Yes Increased cellularity of stromal villi, IUGR

American Journal of Perinatology

Preventable Stillbirths

malperfusion focal fibrous hyaline deposition

with few inflammatory cells, small
focal hematomas
Patient 15 38 Fetal and maternal vascular 7A3 Preventable Stasis in umbilical cord No yes Multiple extensive infarcts, focal
malperfusion chronic inflammatory infiltrate,
hypo/irregular perfusion
Fouks et al.

Patient 16 40 Maternal vascular 2L4 Preventable No No No Focal fibrohyalinosis and coarse IUGR, stasis of blood
malperfusion calcifications vessels in brain
Patient 17 30 Fetal and maternal vascular 2H3 Preventable Early thrombosis of umbilical No Yes Multiple infarcts, inflammatory Stasis of blood vessels in
malperfusion artery cannot be excluded cells, increased number of syncytial brain
knots, extensive fibrous hyaline
deposition, irregular/
hypoperfusion
Patient 18 23 Maternal vascular 2I2 Preventable No Yes No Multiple infarcts, overt abruption—
malperfusion 3 cm (nonacute), hematomas,
fibrous hyaline deposition with
focal inflammatory cells, chronic
abruption
Patient 19 35 Maternal vascular 2L4 Preventable No No No Subchorionic and retrodecidual IUGR
malperfusion hematomas, fibrous hyaline
deposition, features compatible
with IUFD
Patient 20 26 Intrauterine infection þ 2H3 Preventable No Yes Yes Extensive fibrous hyaline deposition
maternal vascular with histiocytic and inflammatory
malperfusion infiltrate, irregular hydropic
features, infarcts, hematomas,
chorioamnionitis, hypo- and
irregular perfusion
Patient 21 28 Intrauterine infection þ 2L4 Preventable No No Yes Areas of acute and chronic IUGR
maternal vascular malperfu- intra- and mostly intervillitis,
sion (may be secondary to congestion, hemorrhage, hemato-
infection) mas, focal acute chorionitis
Patient 22 27 Fetal vascular malperfusion 2L4 Preventable Hypercoiled cord.SUA No No Marked hypercoiled umbilical cord, IUGR
þ mild maternal vascular overt abruption, SUA, focal mono-
malperfusion nuclear inflammatory infiltrate at
chorion, extensive fibrous hyaline
deposition (intra- and intervilli)

Downloaded by: Boston University. Copyrighted material.

 Table 1 (Continued)

Patient GA at Amsterdam criteria SCRN Preventable/ Umbilical Overt Overt Placental findings Positive autopsy
stillbirth classification unpreventable cord findings acute placental findings
abruption inflammation
Patient 23 31 Maternal vascular 2H3 Preventable No Yes Yes Multiple small infarcts, mild basal
malperfusion plate inflammation, features of
focal irregular perfusion, retrodeci-
dual hematoma (chronic)
Patient 24 39 Fetal and maternal vascular 2L4 Preventable Extensive infarction of cord No Yes Extensive infarction of cord, IUGR
malperfusion multiple small placental infarcts,
mild basal plate inflammation, focal
histiocytic infiltrate at villi, focal
fibrous hyaline deposition,
intra-and intervilli, focal calcifica-
tions, focal hydropic changes
Patient 25 31 Fetal and maternal vascular 2L4 Preventable SUA No No SUA, multiple infarcts and IUGR
malperfusion hematomas, extensive fibrinous
hyaline deposition
Patient 26 37 Fetal and maternal vascular 2H3 Preventable Increased number of No No Multiple small placental infarcts
malperfusion syncytial knots, recent
thrombus in umbilical cord
Patient 27 25 Fetal vascular malperfusion 2H3 Preventable Marginal velamentous cord No No Subchorionic hematoma Posterior fossa
insertion hemorrhage
Patient 28 37 Maternal vascular 7A3 Preventable No No No Multiple infarcts, focal intra- and
malperfusion intervillous hyaline deposition, mild
increased number of nucleated
erythrocytes
Patient 29 36 Fetal and maternal vascular 2H3 Preventable Placenta with overt No Yes Dichorionic diamniotic twins,
malperfusion abruption. Marginal fibrohyaline deposits (extensive)
insertion 2 velamentous with foci of histiocytic and
insertion inflammatory infiltrate,
hypo/irregular perfusion
Patient 30 29 Maternal vascular 6F3 Preventable No No No Hypo/irregular perfusion
malperfusion
Patient 31 25 Fetal and maternal vascular 6F3 Preventable Marginal insertion of cord No No Hypo/irregular perfusion, infarcts, Focal microhemor-
malperfusion hypovascular villi, fibrohyalinosis, rhages, hypoxic cellular
focal hematoma changes
Patient 32 26 Maternal vascular 7A3 Preventable No No No Subchorionic hematomas, infarcts,
malperfusion irregular hydropic changes, fibrous
hyaline deposition, irregular
perfusion
Patient 33 25 Maternal vascular 2H3 Preventable Subchorionic hematoma No No Subchorionic hematoma adjacent
Preventable Stillbirths

malperfusion adjacent to the marginal to the marginal insertion

velamentous insertion of
umbilical cord
Marked stasis of umbilical
cord blood vessels
(Continued)
Fouks et al.

American Journal of Perinatology

Downloaded by: Boston University. Copyrighted material.
 Table 1 (Continued)

Patient GA at Amsterdam criteria SCRN Preventable/ Umbilical Overt Overt Placental findings Positive autopsy
stillbirth classification unpreventable cord findings acute placental findings
abruption inflammation

American Journal of Perinatology

Preventable Stillbirths

Patient 34 24 Nonspecific (hypoperfusion) 2L4 Preventable No No No Hypo/irregular perfusion IUGR

Patient 35 42 Nonspecific (hypoperfusion) 2H3 Preventable No No No Fibrous hyaline deposition, mild Recent hemorrhage in
increased number of fetal lateral ventricle, cellular
nucleated RBCs hypoxia
Patient 36 39 Fetal and maternal vascular 2H3 Unpreventable Marginal insertion Yes No Acute abruption
malperfusion
Fouks et al.

Patient 37 23 Maternal vascular 2H3 Unpreventable No Yes No Multiple infarcts and large placental
malperfusion abruption, hematomas, fibrous
hyaline deposition with focal
inflammatory cells
Patient 38 34 Maternal vascular 2H3 Unpreventable Recent stasis in umbilical Yes No Recent retrodecidual hematoma, Brain hypoxia and
malperfusion cord acute abruption edema
Patient 39 35 Maternal vascular 2H3 Unpreventable No Yes No Early subchorionic hematomas, Enlarged thymus,
malperfusion stasis of blood vessels and acute myocardial stasis of
extravasation of erythrocytes, blood vessels
acute abruption (suspected)
Patient 40 23 Maternal vascular 2I2 Unpreventable No Yes No Multiple infarcts, overt abruption,
malperfusion hematomas, fibrous hyaline
deposition with focal inflammatory
cells
Patient 41 35 Maternal vascular 2I2 Unpreventable Recent umbilical cord Yes No Retrodecidual acute hematoma,
malperfusion thrombus focal areas of fibrohyalinosis
Patient 42 34 Maternal vascular 2I2 Unpreventable Recent stasis in umbilical Yes No Acute retrodecidual hematoma and Brain hypoxia
malperfusion cord abruption
Patient 43 35 Maternal vascular 2I2 Unpreventable No Yes No Early subchorionic hematomas, Enlarged thymus
malperfusion stasis of blood vessels and acute
extravasation of erythrocytes
Acute abruption
Patient 44 22 Maternal vascular 2I2 Unpreventable No Yes No Acute abruption, fetal nucleated
malperfusion RBCs show moderately increased
cellular stroma of villi, focal histio-
cytic infiltrate

Abbreviations: GA, gestational age; IUGR, intrauterine growth restriction; RBC, red blood cells; SUA, single umbilical artery.

Downloaded by: Boston University. Copyrighted material.


exact test for small samples for categorical variables and a
two-sided t-test for continuous variables that are normally
distributed. Significance was set at a two-sided p-value
< 0.05. Statistical analyses were performed with SPSS soft-
ware version 22 (IBM, Armonk, NY).
Results
Overall, out of 62,178 deliveries during the study period, 312
stillbirths (0.5%) were identified, of which 228 (73.0%) met
the inclusion criteria. Of these, 110 (48.2%) cases had a
recognized stillbirth etiology, 47 (42.7%) of which were
potentially preventable and 63 (57.3%) of which were unpre-
ventable. In 118 cases (51.8%), there was no recognized
stillbirth etiology (►Fig. 1).
Women with potentially preventable stillbirth were com-
parable for maternal age, pregestational body mass index,
gravidity, parity, and gestational age at the time of stillbirth
diagnosis to women with unpreventable and unexplained
stillbirth (►Table 1). The incidence of maternal medical
complications associated with perinatal mortality (pregesta-
tional and gestational diabetes and chronic hypertension7)
did not differ between the groups. The absence of medical
insurance did not increase the risk of stillbirth.
►Fig. 2 describes the distribution of identifiable (►Fig. 2A)
and potentially preventable (►Fig. 2B) and unpreventable
(►Fig. 2C) stillbirth causes. Thirty-five cases (75%) of all
potentially preventable causes were attributed to placental-
mediated complications. Of these, suggestive placental find-
ings were apparent in 25 patients (71.4%) and comprised
extensive thrombosis of placental or fetal stem vessels
(n ¼ 4) or placental infarction leading to uteroplacental insuf-
Fig. 1 Flow chart of the study cohort.
Preventable Stillbirths Fouks et al.
ficiency and chronic hypoxia (n ¼ 21). Thirteen cases were
complicated by intrauterine growth restriction (estimated
fetal weight < 10th percentile according to local fetal growth
curves)21 with one or more of the following and no other
apparent cause of stillbirth: (1) abnormal Doppler (n ¼ 5), (2)
oligohydramnios < 5th percentile for gestational age (n ¼ 1),
and (3) preeclampsia (n ¼ 3). The mean gestational age at the
time of diagnosis in cases attributed to a placental-mediated
complication was 312/7 weeks of gestation.
The second most common cause of potentially preventa-
ble stillbirth was infections, responsible for four (9%) of all
preventable cases. Two of these four cases occurred shortly
after amniocentesis and presented with maternal sepsis. The
third case was a suspected parvovirus B-19 infection pre-
senting with a recent maternal history of flu-like symptoms
and positive parvovirus immunoglobulin M and immuno-
globulin M (IgG) antibodies. Placental pathology demon-
strated marked focal features of irregular perfusion. The
fourth case was a suspected syphilis infection presenting
in a patient with poor prenatal care with positive venereal
Downloaded by: Boston University. Copyrighted material.
disease research laboratory and Treponema pallidum hemag-
glutination testing and an IgG antibody titer of 1:16. The
median gestational age at the time of diagnosis in these cases
was 263/7 (202/7–322/7) weeks of gestation.
Thirteen cases (27.6%) had more than one potentially pre-
ventable stillbirth cause. The median gestational age at diag-
nosis in these fetuses was 314/7 (20–42) weeks of gestation.
The remaining etiologies identified were uncommon,
each contributing 2 to 6% of all preventable causes.
►Fig. 3 demonstrates the distribution of potentially pre-
ventable, unpreventable, and unknown stillbirth etiologies
stratified by gestational age at diagnosis. The contribution of
American Journal of Perinatology
Preventable Stillbirths Fouks et al.

unpreventable stillbirth was consistently higher than that of

potentially preventable stillbirth throughout all gestational
ages, but the difference did not reach statistical significance.
Potentially preventable stillbirth was most prevalent
between 280/7 and 336/7 weeks of gestation (n ¼ 13, 28.5%).

Discussion
The aim of this study was to identify the contribution of
preventable causes of stillbirth in a large heterogeneous
population and elucidate their associated maternal risk
factors. We found that potentially preventable stillbirth is
responsible for 20% of all stillbirth and approximately 40% of
all stillbirths with a recognized etiology. There were no
demographic or obstetric risk factors for a potentially pre-
ventable etiology. Of all preventable causes, placental-
mediated complications were by far the most frequent cause.
The rate of stillbirth in our study was 5 per 1,000 births.
This rate is similar to previously reported rates in the United
States.22 Our incidence of explained stillbirth of 48% is
similar to previously reported rates23 as well. Our rate of

Downloaded by: Boston University. Copyrighted material.

Fig. 2 Recognized stillbirth causes. (A) Distribution of all identifiable
stillbirth causes. (B) Distribution of potentially preventable stillbirth
causes. (C) Distribution of unpreventable stillbirth causes. Data
presented as n (%).
potentially preventable stillbirth of all stillbirths included in
the cohort is also comparable to that recently reported in
the U.S. population.7
The results of our study are concordant with previous
studies that found placental insufficiency to be the leading
cause of preventable stillbirth,7 and therefore, placental
pathology to be the most useful test for stillbirth evaluation.
Our second most common cause of preventable stillbirth was
infections. Suspected infectious etiologies accounted for 15%
of all stillbirths, a rate similar to that previously reported in
developed countries,19 and 9% of all preventable stillbirths.
Our elaborate infectious workup may explain why our rate of
preventable infectious etiologies was higher than recently
quoted.7 Though infection is known to cause stillbirth,19,24

Fig. 3 Stillbirth causes across gestational ages—distribution of potentially preventable, unpreventable, and unknown stillbirth causes stratified
by gestational age at diagnosis. No statistically significant differences were found among all three gestational age groups.

American Journal of Perinatology


causality is difficult to ascertain and one can argue that
positive acute serologies do not indicate causality. None-
theless, application of a combination of stringent criteria to
the definition of infectious etiology in this study increases
the likelihood of cause and effect.
Our study, though not powered for this outcome, did not
detect any differences in maternal and obstetrical character-
istics between preventable and unpreventable stillbirth
causes. Lack of prenatal care was not associated with poten-
tially preventable stillbirth, a finding supported by a recent
study in the U.S. population.7
The strength of our study is its extensive stillbirth workup
performed in all cases included in the analysis. The exclusion of
cases of intrapartum fetal death from our definition of pre-
ventable stillbirth is an additional strength, since fetal and
neonatal outcomes are highly dependent on the subjective
interpretation of fetal well-being. The main limitation to our
study is that a genetic analysis was not routinely performed as
part of our stillbirth workup. Additionally, variables such as
smoking and drug use, that are known to be associated with
stillbirth,23 may not have been fully accounted for due to partial
reporting. Finally, our classification of potentially preventable
and unpreventable stillbirth causes may be debatable. Though
this is a subjective interpretation and as such may be dispu-
table, we relied on previous categorization systems3,25 and on
the initial causes of fetal death criteria set by the Stillbirth
Collaborative Research Network12 to define our cohort.
In conclusion, according to our findings, one-fifth of still-
birth causes may be preventable. Placental-mediated compli-
cations and infections are the leading potentially preventable
etiologies, accounting for nearly 85% of all preventable causes.
These findings emphasize the uttermost importance of close
sonographic surveillance, appropriate laboratory investiga-
tions, and timely intervention to prevent fetal demise.
Funding
None.
Conflict of Interest
None declared.
References
1 Lawn JE, Lee AC, Kinney M, et al. Two million intrapartum-related
stillbirths and neonatal deaths: where, why, and what can be
done? Int J Gynaecol Obstet 2009;107(Suppl 1):S5–S18
2 Lawn JE, Blencowe H, Waiswa P, et al; Lancet Ending Preventable
Stillbirths Series study group; Lancet Stillbirth Epidemiology
investigator group. Stillbirths: rates, risk factors, and acceleration
towards 2030. Lancet 2016;387(10018):587–603
3 ACOG practice bulletin no. 102: management of stillbirth. Obstet
Gynecol 2009;113(03):748–761
4 Muldoon KA, Galway LP, Nakajima M, et al. Health system
determinants of infant, child and maternal mortality: a cross-
sectional study of UN member countries. Global Health 2011;7:42
5 Frøen JF, Arnestad M, Frey K, Vege A, Saugstad OD, Stray-Pedersen
B. Risk factors for sudden intrauterine unexplained death: epi-
Preventable Stillbirths Fouks et al.
demiologic characteristics of singleton cases in Oslo, Norway,
1986-1995. Am J Obstet Gynecol 2001;184(04):694–702
6 Huang DY, Usher RH, Kramer MS, Yang H, Morin L, Fretts RC.
Determinants of unexplained antepartum fetal deaths. Obstet
Gynecol 2000;95(02):215–221
7 Page JM, Thorsten V, Reddy UM, et al. Potentially preventable stillbirth
in a diverse U.S. cohort. Obstet Gynecol 2018;131(02):336–343
8 Goldenberg RL, Farrow V, McClure EM, Reddy UM, Fretts RC,
Schulkin J. Stillbirth: knowledge and practice among U.S. obste-
trician-gynecologists. Am J Perinatol 2013;30(10):813–820
9 Flenady V, Middleton P, Smith GC, et al; Lancet’s Stillbirths Series
steering committee. Stillbirths: the way forward in high-income
countries. Lancet 2011;377(9778):1703–1717
10 Langston C, Kaplan C, Macpherson T, et al. Practice guideline for
examination of the placenta: developed by the Placental Pathology
Practice Guideline Development Task Force of the College of Amer-
ican Pathologists. Arch Pathol Lab Med 1997;121(05):449–476
11 Khong TY, Mooney EE, Ariel I, et al. Sampling and definitions of
placental lesions: Amsterdam Placental Workshop Group con-
sensus statement. Arch Pathol Lab Med 2016;140(07):698–713
12 Dudley DJ, Goldenberg R, Conway D, et al; Stillbirth Research
Collaborative Network. A new system for determining the causes
of stillbirth. Obstet Gynecol 2010;116(2 Pt 1):254–260
13 Yudkin PL, Wood L, Redman CW. Risk of unexplained stillbirth at
Downloaded by: Boston University. Copyrighted material.
different gestational ages. Lancet 1987;1(8543):1192–1194
14 Caughey AB, Musci TJ. Complications of term pregnancies beyond
37 weeks of gestation. Obstet Gynecol 2004;103(01):57–62
15 Roberts D, Neilson JP, Kilby MD, Gates S. Interventions for the
treatment of twin-twin transfusion syndrome. Cochrane Data-
base Syst Rev 2014;(01):CD002073
16 Papageorghiou AT, Avgidou K, Bakoulas V, Sebire NJ, Nicolaides
KH. Risks of miscarriage and early preterm birth in trichorionic
triplet pregnancies with embryo reduction versus expectant
management: new data and systematic review. Hum Reprod
2006;21(07):1912–1917
17 Harnden A, Mayon-White R, Mant D, Kelly D, Pearson G. Child
deaths: confidential enquiry into the role and quality of UK
primary care. Br J Gen Pract 2009;59(568):819–824
18 Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of
pregnancy: Relationships between bile acid levels and fetal
complication rates. Hepatology 2004;40(02):467–474
19 Reddy UM, Goldenberg R, Silver R, et al. Stillbirth classification–
developing an international consensus for research: executive
summary of a National Institute of Child Health and Human
Development workshop. Obstet Gynecol 2009;114(04):901–914
20 Akolekar R. Re: Risk of fetal loss associated with invasive testing
following combined first-trimester screening for Down syndrome:
a national cohort of 147 987 singleton pregnancies. C. B. Wulff, T. A.
Gerds, L. Rode, C. K. Ekelund, O. B. Petersen, A. Tabor and the Danish
Fetal Medicine Study Group. Ultrasound Obstet Gynecol 2016; 47:
38-44. Ultrasound Obstet Gynecol 2016;47(01):14
21 Dollberg S, Haklai Z, Mimouni FB, Gorfein I, Gordon ES. Birth
weight standards in the live-born population in Israel. Isr Med
Assoc J 2005;7(05):311–314
22 MacDorman MF, Kirmeyer S. Fetal and perinatal mortality, United
States, 2005. Natl Vital Stat Rep 2009;57(08):1–19
23 Frøen JF, Cacciatore J, McClure EM, et al; Lancet’s Stillbirths Series
steering committee. Stillbirths: why they matter. Lancet 2011;
377(9774):1353–1366
24 Moscovis SM, Gordon AE, Al Madani OM, et al. Virus infections
and sudden death in infancy: the role of interferon-γ. Front
Immunol 2015;6:107
25 Group SCRNW; Stillbirth Collaborative Research Network Writing
Group. Causes of death among stillbirths. JAMA 2011;306(22):
2459–2468
American Journal of Perinatology