Stillbirth :Common Causes and Prevention

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Stillbirth, while infrequent, occurs  times more often
than sudden infant death and accounts for a large
proportion of all perinatal losses. In the United States
during , the stillbirth rate was ./ total births
(approximately , stillbirths nationwide). at year, there
were also about , infant deaths (./ live births), and
, neonatal deaths (./ live births).¹ Black women
have more than twice the rate of stillbirth compared to white
women; while some of this increased risk can be attributed to
access to, and quality of, medical care, other factors probably
play a role as well.²
Fetal death can be stratified according to gestational age, into
early losses (– weeks) and late fetal death (> weeks).
Presumably, this approach was used initially to divide those
pregnancies that might be saved (i.e., late losses), from very early
term losses, the majority of which would not be salvageable.
Recent advances in neonatal care make this division somewhat
arbitrary, but the causes of fetal death do vary according to
gestational age. e prevention of a proportion of early losses is
associated with prenatal diagnosis of congenital anomalies and
the availability of abortion. A large proportion is also related to
premature rupture of membranes and infection, complications
that have proven difficult to prevent. Multiple gestations, either
spontaneous or related to reproductive technologies, are also
associated with an increased risk of stillbirth and preterm birth;
these fetal losses occur throughout pregnancy with higher risks
both in early and late pregnancy.
Causes of Stillbirth
Between  and  weeks of gestation, the most common causes
of stillbirth are related to infection ( percent), abruption (
percent) or significant lethal anomalies ( percent);  percent
are unexplained. After  weeks of gestation, the most common
category of stillbirth is that of “unexplained.” (see Table .).³
e proportion of fetal deaths that have no known cause after
complete pathological evaluation increases as gestational age
advances. Deaths unexplained by fetal, placental, maternal, or
obstetric factors—which represent from – percent of all fetal
deaths—are one of obstetrics’ most distressing outcomes.
Medical Risk Factors
Hypertension and diabetes are two of the most common medi-
cal conditions to complicate pregnancy (– percent and –
percent, respectively, see Table ). Historically, both of these
conditions have been shown to be responsible for a significant
proportion of fetal deaths. Optimal management, including
counseling, preconceptual care, and close medical manage-
ment of these conditions has been shown to reduce the risk for
perinatal death to a level only marginally elevated above that
Stillbirth: Common Causes and Prevention Strategies
by Ruth Fretts, MD, MPH
Dr. Fretts is Chair of the Stillbirth Review Committee, Brigham and Women’s Hospital, Boston.
of the general population. Management of patients remains a
challenge, however, because of the increased risks of abruptio
placenta, of intrauterine growth restriction, and of superim-
posed preeclampsia—which often necessitates early delivery.
Other medical conditions associated with an increased risk of
stillbirth include systemic lupus erythematosis, and congenital
and acquired thrombophilias (Table ).
Non-medical Risk Factors
Nationally, black women consistently have had approximately
twice the risk of stillbirth when compared to white women.
Even when evaluating only women who had received adequate
prenatal care, Vintzileos et al, found that African American
women still had twice the risk of stillbirth when compared to
whites. e excess of stillbirth was attributed to higher rates
of diabetes, hypertension, placental abruption, and premature
rupture of membranes.² Given that black women are a relatively
high-risk group for stillbirth, increasing their access to prenatal
care and the identification and management of medical and
socioeconomic risk factors for stillbirth remains important.
Advanced Maternal Age
Advanced maternal age remains an independent risk factor
for stillbirth, even after accounting for medical conditions that
are more likely to occur in older women.⁴ Prior to prenatal
diagnosis, older women were more likely to have a stillbirth
related to congenital anomalies. In recent years, the only type
of stillbirth that was statistically more common in older women
was the “unexplained” category of fetal demise, and these were
likely to occur late in pregnancy.⁵⁸
Obesity
e prevalence of maternal obesity has also been increas-
ing steadily and is associated with an increased risk of fetal
macrosomia and perinatal mortality.⁹¹⁰ e reasons for this
association are speculated to be due to behavioral and socio-
economic issues, as well as obstetric factors. Obese women are
more likely to smoke and to have pregnancies complicated by
gestational diabetes and preeclampsia. However, even when
controlling for these factors, pre-pregnancy obesity remains
a significant risk factor for stillbirth. e association between
Table 1
Common Causes of Stillbirth by Gestational Age
24–27 weeks 28–36 weeks 37+ weeks
Infection 19% Unexplained 26% Unexplained 40%
Abruption 14% Fetal malnutrition 19% Fetal malnutrition 14%
Anomalies 14% Abruption 18% Abruption 12%
From Fretts 2005 Etiology and Prevention of Stillbirth
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elevated pregnancy  and stillbirth at term appears to increase
as the gestation advances. Sleep studies of pregnant women
have shown that obese women spend more time snoring, have
more apnea-hypoxia events, and have more episodes of oxygen
desaturation than non-obese pregnant women.¹¹¹⁴ Snoring
has also been associated with pregnancy-induced hypertension
and fetal growth restriction.¹⁵ In the United States, in addi-
tion to advanced maternal age and low socioeconomic status,
as discussed above, the most prevalent risk factor for stillbirth
is pre-pregnancy obesity.
Prevention of Stillbirth
Prevention of stillbirth requires an ongoing audit process
to evaluate losses in order to assess systematic or common
errors of management. Globally, smoking cessation during
pregnancy is an important area of stillbirth prevention. And,
as previously stated, prenatal diagnosis—with the availability
of abortion, and the minimization of multiple gestations—are
also important strategies to reduce stillbirth (Table ).¹⁶ After
 weeks of gestation, the two most common types of stillbirth
are related to growth restriction and to those that are other-
Table 2
Medical Disorders Associated with Stillbirth Risk
Condition Estimated Stillbirth Rate
All Pregnancies 6–7/1,000
Hypertensive Disorders
chronic hypertension 5–25/1,000
superimposed preeclampsia 52/1,000
PIH/mild preeclampsia 9/1,000
severe preeclampsia 21/1,000
eclampsia 18–48/1,000
HELLP syndrome 51/1,000
Diabetes Mellitus
gestational diabetes 5–10/1,000
type 1 diabetes 6–10/1,000
type 2 diabetes 35/1,000
systemic lupus erythematosus 40–150/1,000
Chronic Renal Disease
mild renal insufficiency 15/1,000/1,000
moderate and severe renal insufficiency 32–200/1,000
Thyroid Disorders
stable treated hyperthyroidism 0–36/1,000
uncontrolled thyrotoxicosis 100–156/1,000
subclinical hypothyroidism 0–15/1,000
overt hypothyroidism 15–125/1,000
cholestasis of pregnancy 12–30/1,000
Modified from Simpson, 2002
Table 3
Maternal Risk Factors/Causes for Stillbirth
Ranked by estimated attributable risk/importance
(developed countries)
1 Congenital/karyotypic anomalies
2 Growth restriction/placental thrombosis
3 Decreased fetal movement
4 Medical diseases (e.g. diabetes, hypertensive disease/
preeclampsia, systemic lupus erythematosus, renal disease, thyroid
disorders, thrombophilias, cholestasis of pregnancy)
5 Congenitally acquired infections (e.g. Group B streptococcus,
parvovirus 19)
6 Smoking
7 Multiple gestation
Adapted from McClure et al, 2006
wise unexplained. e Confidential Inquiry into Stillbirths
and Infant Death of Northern Ireland found that the failure
to adequately diagnose and manage fetal growth restriction
was the most common error, followed by failure to recognize
additional maternal medical risk factors.¹⁷ Given that deaths
of intrauterine growth-restricted fetuses represent one of the
most common types of stillbirths, a significant opportunity
remains to improve outcomes. Assessment of fetal growth by
ultrasound should be considered for at-risk patients. A custom-
ized growth chart more readily identifies the growth-restricted
fetus, and reduces “false-alarms” in the constitutionally small
fetus.¹⁸ Ideally, serial ultrasounds should be reported together
so that the history of intrauterine growth over time can be more
readily appreciated. e threshold to perform an ultrasound
in the obese patient should be low, since fetal growth is often
difficult to estimate clinically.
Risk factors of unexplained stillbirth include advanced ma-
ternal age, pre-pregnancy obesity, low educational attainment,
and—in some studies—primiparity.⁵⁸ e risk of unexplained
stillbirth rises after  weeks, and more so for primiparous
women. Women – years of age have a / risk of still-
birth after the th week of pregnancy, compared to / for
women less than  years of age. e risk is higher for women
age  or older, where / women will experience a stillbirth
after week . Currently, no guidelines specifically address
women of advanced maternal age later in pregnancy, but a
decision analysis predictably estimates that, while a strategy of
antepartum testing could reduce late stillbirths, it would also
lead to a higher intervention rate, including an increased risk
of induction and cesarean section.²⁰
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Another area of prevention that has not previously been em-
phasized is the role of kick counting. In a quality improvement
study in Massachusetts (Brigham and Women’s Hospital,
and Newton Wellesley Hospital), we evaluated the outcomes
of pregnancies complicated with the complaint of decreased
fetal movement. e rate of stillbirth in those pregnancies that
were complicated with decreased fetal movement was four-fold
above the general population. While providers were prompt at
referring patients for evaluation with this complaint,  percent
of women waited two days or more before reporting to their
provider that they noticed decreased fetal movement. e most
common evaluation was a non-stress test ( percent); only 
percent of women were evaluated with an ultrasound. In the
pregnancies that reported decreased fetal movement and ended
in a stillbirth,  percent were severely growth restricted. A
strategy of evaluating fetal growth with an ultrasound could
potentially increase the opportunity of detecting growth restric-
tion prior to fetal demise. ere was also a disappointing aspect
of the study: of  women who had stillbirths after reporting
decreased fetal movement, three had had prompt and reassur-
ing antepartum testing—but had stillbirths anyway. All three
cases involved additional risk factors that were overlooked,
including unidentified growth restriction at term, post-dates,
and a previous stillbirth.
Summary
Clinicians need to be able to assess each patient’s risk for adverse
outcomes, including stillbirth, and should have a low thresh-
old to evaluate fetal growth in at-risk pregnancies. Decreased
fetal movement represents a high-risk condition, as does late
pregnancy. A strategy of antepartum testing in patients with
increased risk should serve to decrease the risk factors of late
fetal loss, but is associated with higher intervention rates and
their inherent risks. ■
Continued from previous page
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Stillbirth: Common Causes and Prevention Strategies (continued)
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