DOI: 10.1111/tog.

12708 2021;23:48–59
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

Care in pregnancies subsequent to stillbirth

or perinatal death
MRCOG, *
a b c
Nicole Graham Louise Stephens RM, Alexander EP Heazell PhD MRCOG
a
Consultant Obstetrician, Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology,
Medicine and Health, University of Manchester, and Department of Obstetrics, St Mary’s Hospital, Manchester M13 9WL, UK
b
Research Midwife, Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and
Health, University of Manchester, and St Mary’s Hospital, Manchester M13 9WL, UK
c
Professor of Obstetrics and Honorary Consultant Obstetrician, Maternal and Fetal Health Research Centre, Division of Developmental Biology and
Medicine, Faculty of Biology, Medicine and Health, University of Manchester, and Department of Obstetrics, St Mary’s Hospital,
Manchester M13 9WL, UK
*Correspondence: Nicole Graham. Email: nicole.graham@mft.nhs.uk

Accepted on 15 May 2020. Published online 10 December 2020.

Key content information to be covered in such an appointment in a

 Pregnancies following stillbirth have an increased risk of adverse
outcome, including a 4.8-fold increased risk of stillbirth.
 Risk factors for stillbirth include obesity, smoking, advanced
maternal age, fetal growth restriction, hypertension and diabetes.
 Increased risk of medical problems may result from recurrent
placental pathologies or genetic conditions or persistent maternal
disease; thus, care for a subsequent pregnancy should commence
with investigation of the index stillbirth.
 Parents also require additional psychological support to navigate
mixed emotions, particularly anxiety, about the development of
pregnancy complications.
 Antenatal care in a subsequent pregnancy after stillbirth should
ideally be delivered by a multidisciplinary team to provide
continuity of physical and psychological care.
Learning objectives
 To improve understanding of the importance of a
pre-conception/early pregnancy appointment and the key
pregnancy after stillbirth.
 To know what information can be gained from postnatal
investigations and the placental histology report and the
relationship between this information and a subsequent pregnancy
after stillbirth.
 To be able to describe an example of a model of care used to
address medical and psychological needs of parents in
subsequent pregnancy.
Ethical issues
 Failing to appreciate the medical and psychological significance of
a history of stillbirth may lead to suboptimal antenatal care that
does not meet women’s needs.
 Lack of robust evidence may lead to prescription of medication
without clear evidence of benefit.
Keywords: adverse pregnancy outcome / placental histopathology /
small for gestational age / stillbirth / subsequent pregnancy

Please cite this paper as: Graham N, Stephens L, Heazell AEP. Care in pregnancies subsequent to stillbirth or perinatal death. The Obstetrician & Gynaecologist
2021;23:48–59. https://doi.org/10.1111/tog.12708

rates, which have fallen at a faster pace.4 Definitions of

Stillbirth
Stillbirth, the death of a baby before birth or during labour,
has been described as a worldwide epidemic.1 With
2.6 million stillbirths estimated in 2015,2 its burden is
greatly underappreciated. Ninety-eight percent of stillbirths
occur in low- and middle-income countries (LMICs).
Importantly, the aetiology of stillbirth differs between high-
income countries (HICs) and LMICs. For example, the
estimated proportion of intrapartum stillbirths varies from
approximately 10% in HICs to 60% in South Asia;3 this is
closely related to access to high-quality antenatal and
intrapartum care. Globally, the rate of stillbirth reduction
has remained beneath that of infant and maternal mortality
stillbirth vary internationally, with the lower gestational age
limit used to define stillbirth ranging between 16 and 28
weeks of gestation.5 In the UK, stillbirth is defined as ‘a baby
delivered with no signs of life known to have died after 24
completed weeks of pregnancy.’6
There is greater than six-fold variation in stillbirth rates
between HICs (from 1.3 per 1000 total births in Iceland to
8.8 per 1000 births in Ukraine). There is also wide variation
in the rate of reduction in stillbirth rates in HICs. Between
2000 and 2015 the annual rate of reduction in the UK was
1.4% per year, placing it in the lowest third of HICs, i.e. those
with the slowest rates of reduction.7 In the UK in 2017, there
were approximately 2800 stillbirths, which equates to roughly

48 ª 2020 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any
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1 in 270 pregnancies after 24 weeks of gestation. Six of the 49
HICs (Andorra, Croatia, Denmark, Finland, the Netherlands
and Iceland) showed third trimester stillbirth rates of 1 per
500 births or lower.7 Despite reductions in stillbirths in
recent years, this strongly suggests that more can be done in
the UK to reduce stillbirth rates.
The Lancet’s ‘Ending Preventable Stillbirth’ series1-4, set a
target of 12 stillbirths per 1000 total births or fewer by 2030
for all countries. It encourages HICs who have already met
this target to continue to reduce their stillbirth rate and, since
impoverished or socially excluded women are among those at
highest risk, to close inequality gaps. One approach to
reducing stillbirth is to identify pregnancies with risk factors
for stillbirth and implement increased surveillance and/or
directed intervention to mitigate the additional risks.
Risk factors for stillbirth in high-income
countries
Numerous risk factors for stillbirth in HICs have been
identified through observational studies and subsequent
meta-analyses (Table 1). Risk factors such as low socio-
economic status, advanced maternal age, essential
hypertension, pre-eclampsia, antepartum haemorrhage
(APH) and fetal growth restriction (FGR) were examined
in these studies; their hazard ratios (HRs), odds ratios (ORs)
and population attributable risks (PARs) are shown in
Table 1. Except for APH and FGR, the ORs for these risk
factors have a range of 1.2–3.5-fold increased risk of stillbirth.
Critically, the Stillbirth Collaborative Research Network
study in the USA8 found that only 18% of stillbirths
occurred in women with risk factors identified at booking.
The authors concluded that pregnancy history was the
strongest risk factor for stillbirth.
A history of previous stillbirth is a recognised risk factor
for stillbirth in a subsequent pregnancy.9–11 As these studies
analysed population-level data, recurrence risks for
individual causes of stillbirth could not be examined.
Nevertheless, comparison with other risk factors
demonstrates that prior stillbirth has a comparable or
greater risk for stillbirth than many other risk factors that
already have robust recommendations for additional
antenatal surveillance (e.g. diabetes12).
Addressing many of these risk factors is challenging; some
risk factors such as obesity, advanced maternal age and
cigarette smoking require broad public health initiatives,
reaching beyond the remit of UK National Health Service
(NHS) maternity services. For example, women must be
aware of risk factors for stillbirth, such as advanced maternal
age, illicit drug use and treatment of pre-existing medical
conditions, to enable informed decision-making with regards
to childbearing. The focus of strategies from a maternity care
perspective is on women at highest risk of stillbirth and to
ª 2020 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.
Graham et al.
institute appropriate interventions. For example, both Hirst
et al.13 and Gardosi et al.14 demonstrate the importance of
antenatal detection of small-for-gestational-age (SGA)
infants (as a proxy for FGR) because when this is identified
during pregnancy, the risk of stillbirth is considerably lower
than when SGA is undetected. To date, efforts to reduce
stillbirth have been directed towards additional monitoring
in high-risk populations to detect FGR.15 Thus, an effective
strategy to reduce stillbirth in HICs might be to identify
women at high risk and provide them with optimal care.
Risk of stillbirth and other complications
in a subsequent pregnancy
Stillbirth in a previous pregnancy is a risk factor for stillbirth
in a subsequent pregnancy (Table 1). A large systematic
review and meta-analysis of 16 studies,16 including
3 412 079 pregnancies in HICs, demonstrated a stillbirth
rate in 2.5% of women with a previous history of stillbirth
compared with a rate of 0.4% when previous pregnancy
resulted in a livebirth. This gave a pooled OR of 4.8 (95%
confidence interval [CI] 3.77–6.18). In addition, a case
control study in the Grampian region of Scotland17 found
that previous stillbirth also increases the risk of other adverse
pregnancy outcomes, such as pre-eclampsia (OR 3.1, 95% CI
1.7–5.7), placental abruption (OR 9.4, 95% CI 4.5–19.7), low
birthweight (OR 2.8, 95% CI 1.7–4.5), prematurity (OR 2.8,
95% CI 1.9–4.2) and intervention at delivery with induction
of labour (OR 3.2, 95% CI 2.4–4.2), instrumental delivery
(OR 2.0, 95% CI 1.4–3.0), elective caesarean section (OR 3.1,
95% CI 2.0–4.8) and emergency caesarean section (OR 2.1,
95% CI 1.5–3.0). These studies were not able to identify
whether the risks of complications in subsequent pregnancy
were affected by the cause of the stillbirth, although –
interestingly – many of the associated pathologies are
associated with abnormal placentation.
Although the risk of stillbirth is increased in subsequent
pregnancy after stillbirth, few studies have investigated the
cause of recurrent stillbirth. Interpretation of published data
is hampered by small study size, the use of different
classification systems, a lack of consensus in terminology
and limited information on the cause of index stillbirth. A
recent US cohort study,18 which included 3003 women,
found that stillbirth recurrence was more likely when a
maternal or placental condition occurred in the second
trimester of the index pregnancy (13–24 weeks of gestation).
This study found recurrent fetal causes were less common.
There was a trend towards increased risk of recurrence in
women with diabetes mellitus (4% versus 3.5%) or
hypertension (5% versus 3%). Nijkamp et al.19
demonstrated an association between cause of death in the
index pregnancy and cause of death in the subsequent
pregnancy in half of the cases examined. The relationship was
49
 Care in pregnancies after stillbirth

Table 1. Risk factors for stillbirth

Hirst et al., 201813 Flenady et al., 201183 Gardosi et al., 201314

Study

Brazil, China, India, Italy, Meta-analysis of

Kenya, Oman, UK, USA. international studies UK

Setting HR (95% CI) PAR (%) OR (95% CI) PAR (%) RR (95% CI) PAR (%)

Maternal medical factors

Diabetes mellitus - - 2.9 4.0 3.9 (1.7–8.9) 2.0

Essential hypertension 4.0 (2.7–5.9) 5.5 2.6 13.6 1.4 (0.8–2.5) -

HIV/AIDS 4.3 (2.0–9.1) 0.3 - - - -

Pre-eclampsia 1.6 (1.1–3.8) 1.4 1.6 (1.1–2.2) 3.1 2.8 (1.5–5.1) -

Severe pre-eclampsia with antepartum haemorrhage 4.2 (1.3–13.6) 2.2 - - - -

Severe pre-eclampsia with no antepartum 2.8 (1.5–5.1) 1.6 - - - -

haemorrhage

Previous stillbirth - - 2.6 (1.5–4.6) 0.8 3.3 (1.8–6.0) 8.0

Fetal/pregnancy factors

Multiple pregnancy 3.3 (2.0–5.6) 7.4 - - - -

Birthweight < 3rd centile/<10th centile 4.6 (3.4–6.2) 11.1 3.9 (3.0–5.1) 23.3 7.8 (5.6–10.9) 22.2

SGA at birth – FGR not detected antenatally 5.0 (3.6–7.0) 9.4 - - 6.5 (4.9–8.4) 32.0

SGA at birth – FGR detected antenatally 3.5 (1.9–6.4) 2.2 - - 3.4 (2.2–5.2) 6.2

Post term pregnancy >42 weeks of gestation - - 1.3 (1.1–1.7) 0.3 - -

Maternal–sociodemographic factors

Age > 40 years/>45 years 2.2 (1.4–3.7) 3.0 2.9 (1.9–4.4) - 1.2 (0.9–1.6) -

Primiparity - - 1.4 (1.3–1.42) 14.7 1.8 (1.3–2.5) 21.3

Body mass index >30/>35 - - 1.6 (1.3–1.9) 1.6 (1.1–2.4) 4.2

Smoking - - 1.4 (1.2–1.46) 14.7 2.5 (1.7–3.6) 9.4

No antenatal care accessed - - 3.3 (3.1–3.6) 0.7 - -

Low socio-economic status 1.6 (1.2–2.1) 9.7 1.2 (1.0–1.4) 9.0 1.6 (1.3–2.0) -

Single marital status 2.0 (1.4–2.8) 4.8 - - - -

Illicit drug use - - 1.9 (1.2–3.0) 2.1 - -

FGR = fetal growth restriction; HR = hazard ratio; OR = odds ratio; PAR = population attributable risk; RR = relative risk, SGA = small for gestational
age

50 ª 2020 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

more evident in stillbirths at early gestations. Owing to the
small population size, they were unable to establish the risk of
recurrence of specific causes, but cited placental bed
pathology, placental pathology and preterm prelabour
rupture of membranes as relevant causes. Monari et al.20
conducted a larger prospective study and concluded that the
risk of adverse pregnancy outcome (defined as perinatal
death, FGR, preterm birth at less than 34 weeks of gestation,
hypoxic ischaemic encephalopathy or respiratory distress) is
more frequent when stillbirth was related to placental
vascular disorder (39.6%) than when stillbirth was related
to a different cause (OR 2.1, 95% CI 1.2–3.8). Taken
together, these studies suggest that placental dysfunction,
particularly that originating from maternal vascular
malperfusion, may underlie recurrent adverse pregnancy
outcome. Other causes, such as umbilical cord occlusion or
fetal–maternal haemorrhage may be less likely to recur;
therefore, accurate investigation and classification of the
cause of stillbirth is important to inform care in subsequent
pregnancy. This would allow individualised antenatal care
and increased surveillance for those who need it and would
potentially reduce anxiety and unnecessary intervention in
women with a low risk of recurrence.
Establishing cause of stillbirth and
classification of stillbirth
Stillbirth classification is important to direct care in a
subsequent pregnancy. Classification of stillbirth has recently
been reviewed by Allanson et al.21–23 to coincide with the
launch of the World Health Organization (WHO)’s ICD-PM
(application of the International Classification of Diseases
during the perinatal period) classification system. Currently,
many different classification systems are used worldwide – 81
between 2009 and 2014, which makes data analysis and
comparison extremely difficult. There is also huge variation
in the utility of classification systems; for example, only a
small number distinguish between intrapartum and
antepartum stillbirth and a high proportion, approximately
80%, excluded FGR/SGA in their list of causes of stillbirth
despite the known strong association.24,25 Current, common
systems include Aberdeen,26 Wigglesworth,27 ReCoDe
(Classification of stillbirth by Relevant Condition at
Death),28 PSANZ-PDC (Perinatal Society of Australia and
New Zealand Perinatal Death Classification),29 CoDAC
(Causes of Death and Associated Conditions)30 and
Tulip,31 the characteristics of which are summarised
in Table 2.
The proportion of stillbirths classified as ‘unexplained’
varies greatly depending on the classification system used.
Aberdeen and Wigglesworth have the highest proportion of
unexplained stillbirths (44.3% and 50.2%, respectively), while
ReCoDe has the lowest proportion at approximately 15%.32
ª 2020 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.
Graham et al.
Importantly, the inclusion of placental histology in the
classification of stillbirth reduces the number of stillbirths
classified as ‘unexplained’.33 This may be because, in 11–65%
of stillbirth cases, placental lesions cause or are associated
with fetal death.34 The most recent Perinatal Mortality
Surveillance Report, released in June 2019 and covering all
births during 2017, reported on 2840 stillbirths. The cause of
death by CoDAC was recorded as ‘unknown’ in 34.6% of
cases. Other causes of stillbirth included placental problems
(31.8%) and congenital anomalies (9.2%). Intrapartum
complications accounted for 1.8% of stillbirths.35
Importantly, classification of stillbirth relies upon
information obtained at the time of stillbirth from the
maternal history and investigations.
Post mortem examination, placental examination and
cytogenetic analysis are the most valuable investigations
available after a stillbirth. A study of 1025 stillbirths in the
Netherlands36 found placental examination helped to
determine the cause of death in 95%, post mortem
examination provided cause of death information in 72%
of cases and cytogenetics in 29% of cases. A post mortem
following stillbirth provides new information that changes
the diagnosis in between 9% and 34% of stillbirths, provides
some additional information in 22% of stillbirths and
confirms the clinical diagnosis in between 49% and 58% of
stillbirths.37–40 Histopathological examination of the placenta
by a pathologist provides useful information in at least 50%
of stillbirths and reduces the reporting of ‘unexplained’
stillbirth from 30% to 10%.34 Haematological and
immunological investigations, especially in patients who
have experienced other forms of pregnancy loss, can
sometimes identify treatable conditions such as
antiphospholipid antibody syndrome or inflammatory
conditions associated with underlying pathology (Table 3).
Observed changes can be related to placental structure and
placental function. Placental lesions can be broadly categorised
into four groups: inflammatory, obstructive, disruptive and
adaptive. Obstructive (e.g. maternal and fetal vascular
malperfusion) and adaptive lesions (villous dysmaturity) are
most commonly seen in SGA stillbirths and FGR live births.41
Importantly, the type of placental lesion varies with gestational
age: ascending infection is most common in the mid-trimester,
peaking at 22 weeks of gestation, and maternal vascular
malperfusion is most common in the early third trimester.42
Inflammatory lesions, such as chronic histiocytic intervillositis
(CHI) and villitis of unknown aetiology (VUE), are associated
with stillbirth. Although these are comparatively infrequent
(incidence of CHI is 0.06% of pregnancies;43 VUE incidence is
5.1%44), they are important findings because they are thought
to be recurrent – particularly CHI, which has a recurrence rate
of 80% in subsequent pregnancy and needs specific drug
therapy.45 Interpretation of histopathological findings should
be carefully related to clinical history since lesions can also be
51
 Care in pregnancies after stillbirth

Table 2. Characteristics of some commonly used classification systems for stillbirth

Timing of SB
Classification Associated (antepartum/ FGR Country
system Year Format Factors included conditions intrapartum) included Population origin

Aberdeen 1954 Hierarchical Maternal, fetal No No No SB and NND UK

No placental

Wigglesworth 1980 Hierarchical Maternal, fetal No Yes No SB and NND UK

No placental

ReCoDe 2005 Hierarchical Maternal, fetal Yes Yes Yes SB UK

Placental

PSANZ-PDC 2004 Mostly hierarchical Maternal, fetal Yes Yes Yes SB (20 weeks) Australia
Limited placental and NND

Tulip 2006 Mostly hierarchical Maternal, fetal No No No SB (16 weeks) Netherlands

Placental and NND

CoDAC 2009 Partly hierarchical Maternal, fetal Yes Yes Yes SB and NND Norway
Placental

CoDAC = Causes of Death and Associated Conditions; FGR = fetal growth restriction; NND = neonatal death; PSANZ-PDC = Perinatal Society of
Australia and New Zealand Perinatal Death Classification; ReCoDe = Relevant Condition at Death; SB = stillbirth

seen in apparently healthy pregnancies. Others are associated
with multiple unrelated conditions, such as fetal thrombotic
vasculopathy (which has been related to cord abnormalities),
cytomegalovirus and gestational diabetes.46 Table 4
summarises placental lesions associated with stillbirth.
Care in pregnancies after stillbirth
There is little high-level evidence to direct the management of
pregnancies following stillbirth.47 This absence of evidence
results in considerable variation in care for parents. An online
survey of UK maternity units48 demonstrated that a small
minority had specific written guidance to support care
delivery in a subsequent pregnancy following stillbirth or
neonatal death and that most parents did not receive
adequate emotional and psychological support. This, in
turn, increases the risk of poor health outcomes during
future pregnancies. An international multi-language web-
based survey of 2716 parents49 showed similar findings, with
wide variation in care received across geographic regions.
Sixty-seven percent of parents received additional antenatal
visits and 70% received additional ultrasound scans;
however, only 10% had access to a bereavement counsellor.
A meta-synthesis 50,51 demonstrated that a relationship
with healthcare professionals, dedicated antenatal clinics,
psychological support and continuity of care are important
when caring for women and their families in a subsequent
pregnancy. Thus, care in the subsequent pregnancy not only
needs to focus on the increased risk of adverse pregnancy
outcome, but also on the emotional and psychosocial effects
on parents that persist into the subsequent pregnancy. In
particular, parents are at increased risk of intense anxiety,
depression, fear, complex emotional responses and refrain
from forming bonds with the unborn baby as a coping
mechanism.52 Providing this level of emotional care requires
specially trained staff, bereavement counsellors and time,
which can rarely be adequately provided in a busy ‘routine’
antenatal clinic.
Care in a subsequent pregnancy following stillbirth should
ideally start following the index stillbirth, with access to
appropriate investigations, perinatal review and a
consultation with an obstetrician who will offer continuity
of care. This postnatal consultation following the stillbirth
gives the opportunity for investigation results to be discussed,
modifiable risk factors to be reviewed and for plans for a
subsequent pregnancy to be made, including dietary and
supplementation advice, smoking cessation and weight loss
prior to conception.53 There is no ‘ideal’ inter-pregnancy
interval to reduce adverse outcome in a subsequent
pregnancy; in particular, the risk of stillbirth/SGA/pre-
eclampsia in HICs is not altered by short or long inter-
pregnancy intervals.54,55 Many families embark on a
pregnancy within 12 months of the stillbirth; indeed, 66%
of parents who participated in a large international survey
reported conceiving their subsequent pregnancy within
1 year of the stillbirth.49

52 ª 2020 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

Table 3. Haematological and immunological investigations after stillbirth in specific clinical contexts
Test Association
Inherited thrombophilia screen (factor V Leiden Maternal or fetal vascular
mutation, prothrombin gene variant, protein S malperfusion of placenta
deficiency, protein C deficiency, antithrombin
deficiency)
Acquired thrombophilia screen (anticardiolipin Maternal vascular
antibodies, lupus anticoagulant) malperfusion, CHI, VUE
Autoimmune screen (antinuclear antibodies) CHI, VUE
CHI = chronic histiocytic intervillositis; VUE = villitis of unknown aetiology
Care in a pregnancy after stillbirth should be
individualised, taking into consideration the cause of
stillbirth and the wishes of the woman and her family.
Therefore, efforts should be made to obtain the results of
investigations into the cause of stillbirth, or to undertake a
verbal autopsy to deem the most likely cause in the absence of
other information.56 Women who have a history of stillbirth
should be referred for consultant-led care and a plan of care
made with the woman in early pregnancy. This plan of care
should include screening for established risk factors, such as
smoking and gestational diabetes, with carbon monoxide
detectors and oral glucose tolerance tests, respectively.57,58
Importantly, women who have had a stillbirth are more likely
to stop smoking than women whose prior pregnancy ended
in a livebirth.59 If a woman stops smoking before 16 weeks of
gestation, risk is the same as that for nonsmokers; therefore,
early intervention reduces the risk of adverse outcome.60
Where indicated, drug therapy to reduce recurrent placental
complications (e.g. aspirin) should be commenced in the
first trimester.
Models of care: the role of a specialist
antenatal service
As with other conditions associated with higher risk of
complications (e.g. previous preterm birth, diabetes), a
specialist clinical service improves clinical outcome and
parents’ experience. There are few dedicated clinical services
(‘Rainbow Clinics’) that care for women in a subsequent
pregnancy after stillbirth or neonatal death.48 Models of
multidisciplinary continuity of care combined with regular
antenatal surveillance are associated with improved clinical
outcomes, particularly a reduction in preterm birth and
improved patient experience.61 A recommended pathway for
care is shown in Figure 1. In this pathway, planning for a
subsequent pregnancy commences with the investigation of
ª 2020 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.
Graham et al.
Notes
Antithrombin, protein C and S levels can be affected by pregnancy.
Best performed ≥6 weeks postnatal
Association with inherited thrombophilia and stillbirth is
contentious, particularly when women are heterozygous
If positive, tests should be repeated after 6–12 weeks to confirm
whether levels remain elevated
Autoimmunity is more common in women with VUE and CHI
Autoimmunity is more common in women with VUE and CHI
the index stillbirth and follow-up at a postnatal appointment,
commencing appropriate treatment early in the subsequent
pregnancy and implementation of screening for SGA/FGR
with involvement of other relevant specialist services (e.g.
maternal medicine clinics, fetal medicine unit). As pregnancy
progresses, a plan for birth should be developed, addressing
the wishes of the woman and her family.
Role of ultrasound surveillance in
pregnancies after stillbirth
Women who have had a stillbirth are at increased risk of
giving birth to an SGA infant (OR 6.4 95% CI 0.78–52.662).
The Royal College of Obstetricians and Gynaecologists’
(RCOG) guideline for the detection of SGA fetus63
recommends that women with a history of stillbirth should
have ultrasound measurement of fetal biometry. Assessment
of fetal growth is recommended to be undertaken on
multiple occasions because serial fetal biometry to generate
an estimated fetal weight with growth velocity plotted on a
growth chart has the best detection rate for SGA and FGR.63
Practitioners should be aware that while ultrasound scans
provide a degree of reassurance for parents, this reassurance
is short lived. Parents may also be anxious prior to scans
because the in utero fetal death in their previous pregnancy
would likely have been confirmed by ultrasound scan.52
Other methods of screening for SGA or FGR, or to identify
increased risk of stillbirth, include measurement of blood
flow through the umbilical or uterine arteries by Doppler
ultrasound. This stems from observations that abnormal
blood flow through the uterine artery in the second trimester
is associated with an increased risk of developing pre-
eclampsia and FGR, both of which are associated with
abnormal placentation and stillbirth.64,65 In addition,
ultrasound has also been used to assess placental structure;
this may be relevant because placental disorders are
53
 Care in pregnancies after stillbirth

Table 4. Placental lesions associated with stillbirth42–44

Category Placental lesions Associated with Subsequent pregnancy

Maternal vascular Placental hypoplasia Fetal growth restriction Assess maternal

malperfusion Placental weight <10th centile  thin cord <10th centile Pre-eclampsia cardiovascular status
Infarction Preterm and term stillbirth Glucose tolerance test
Crowding and congestion of villi, migration of Spontaneous preterm birth Thrombophilia screen
neutrophils into intervillous space, compressed or Renal function
obliterated intervillous space, increased fibrin Low dose aspirin
deposition, pyknosis and karyorrhexis of trophoblast, Preconception weight loss
ghost villi 10–25% recurrence risk
Acute, subacute or chronic
Retroplacental haemorrhage
Blood accumulation on maternal surface, compression of
overlying parenchyma
Distal villous hypoplasia
Paucity of villi in relation to surrounding stem villi, villi thin
and elongated, increased syncytial knots
Focal or diffuse
Accelerated villous maturation
Small or short hypermature villi for gestation, increased
syncytial knots, increased intervillous fibrin
Mild, moderate or severe

Fetal vascular Thrombosis Fetal growth restriction Thrombophilia screen

malperfusion Arterial or venous Preterm and term stillbirth Glucose tolerance test
Acute, subacute or chronic
Fibrin deposits, endothelial oedema, iron deposits in
basement membrane, thrombi attached to vessel wall,
fibrosis in proximal villi, calcification
Avascular villi
Loss villous capillaries, fibrosis of villous stroma, small,
intermediate or large foci
Villous stromal-vascular karyorrhexis
Rupture of fetal vessels in primary villi with haemorrhage
and inflammatory cells
Stem vessel obliteration
Oedema in fetal vessel wall, obliteration vessel lumen
Intramural fibrin deposition

Delayed villous Reduced vasculosyncytial membranes Term stillbirth Glucose tolerance test
maturation Continuous cytotrophoblast layer Preconception weight loss
Centrally placed capillaries Unknown recurrence risk
Focal or diffuse

Ascending uterine Maternal stage 1: acute subchorionitis or chorionitis Spontaneous preterm birth If spontaneous preterm birth with
infection Maternal stage 2: acute chorioamnionitis Adverse neonatal outcome chorioamnionitis, 10–25%
Maternal stage 3: necrotising chorioamnionitis recurrence risk
Fetal stage 1: chorionic vasculitis or umbilical phlebitis
Fetal stage 2: involvement of umbilical vessels
Fetal stage 3: necrotising funisitis

Immune inflammatory Villitis of unknown aetiology Fetal growth restriction Maternal autoimmune testing
lesions Low or high grade Miscarriage Preconception weight loss
Lymphohistiocytic  occasional plasma cells Preterm stillbirth Low dose aspirin
Chronic villitis  LMWH
Fibrous villi, obliterated fetal vessel, perivillous fibrin  Immunosuppressive therapy
Intervillositis Villitis of unknown aetiology,
Acute: neutrophils in villi/intervillous space, fibrin 25–50% recurrence risk

54 ª 2020 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

Table 4. (Continued)
Category Placental lesions
Chronic: small placenta, diffuse intervillous invasion of
lymphocytes, macrophages and oesinophils, villous
necrosis, perivillous fibrin
Histiocytic: small placenta, diffuse intervillous invasion of
histiocytes
LMWH = low-molecular-weight heparin
implicated in recurrent pathologies.34 Abnormal uterine or
umbilical artery flow with a thickened placental disc are
associated with complications such as FGR and stillbirth.46
This approach may be effective in a high-risk population.
Toal et al.66 examined the predictive accuracy of a
combination of maternal serum screening (for serum
alphafetoprotein and human chorionic gonadotrophin at
16–18 weeks of gestation), second trimester uterine artery
Doppler and placental morphologic condition (shape and/or
texture). They found no cases of unexpected stillbirth in the
cohort and no cases of severe early-onset FGR after a normal
placental profile. Combining ≥2 abnormal components of the
test predicted 14 of 19 pregnancies that developed severe
early-onset FGR (sensitivity 74%) and 15 of 22 pregnancies
that ended in stillbirth (sensitivity 68%). In another
population, Viero et al.67 showed the combination of
abnormal uterine artery Doppler, abnormal placental shape
and echogenic cystic lesions was strongly predictive of
stillbirth with a sensitivity of 81% and a positive predictive
value of 52%. Therefore, assessment of uterine artery Doppler
and placental size, shape and echotexture may be of benefit in
identifying women at high risk of adverse outcome in a
subsequent pregnancy so that surveillance can be put in place
(e.g. earlier or more frequent ultrasound scans). Of these
different elements, the uterine artery Doppler appears to be
the most informative component of this screen.68
Specific pharmacological treatments
Pharmacological interventions may be directed at optimising
maternal health or reducing the risk of placental disorders.
Maternal medical conditions should be treated with
therapeutic agents that are effective and safe in pregnancy.
Vitamin D should be prescribed according to guidelines
from the National Institute of Health and Care
Excellence (NICE).69
The most commonly used intervention to reduce recurrent
stillbirth from placental causes is aspirin: 150 mg once at
night, ideally commenced before 16 weeks of gestation and
continued until at least 36 weeks (when some trials cease
ª 2020 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.
Graham et al.
Associated with Subsequent pregnancy
Chronic histiocytic intervillositis,
75–90% recurrence risk
use). This is recommended because aspirin commenced
before 16 weeks of gestation reduces the risk of perinatal
death (relative risk [RR] 0.41, 95% CI 0.19–0.92).70 Evidence
from a subsequent meta-analysis71 also suggests that higher
doses of aspirin (e.g. 150 mg rather than 75 mg) are more
effective at preventing FGR and pre-eclampsia. Although
there are no data specifically on women whose previous
pregnancy ended in stillbirth, this is thought to be beneficial
for women whose stillbirth was associated with
placental disease.
There is currently no high-grade evidence to support the
use of low-molecular-weight heparin (LMWH) with the
primary aim to prevent fetal complications in women with a
history of stillbirth. However, it should be used in women at
high risk of maternal venous-thromboembolism. Some
smaller studies show a potential benefit; one Indian study72
showed that prophylactic LMWH commenced before
15 weeks of gestation substantially reduced admissions to
the neonatal intensive care unit (NICU) by 80%. However,
the EPPI73 and TIPPS74 studies, which were both large,
multicentre, randomised controlled trials, failed to
demonstrate benefit in fetal outcomes. Presently, it should
be reserved for women with antiphospholipid antibody
syndrome or CHI.
CHI is a rare placental lesion associated with poor obstetric
outcome and has a high risk of recurrence in subsequent
pregnancies (80%). One prospective multicentre study75
described the efficacy of different treatment regimes: the
number of live births increased in the treatment group from
32% to 67% with quadruple therapy of aspirin, LMWH,
prednisolone and hydroxychloroquine and resulted in better
pregnancy outcomes than aspirin alone.
Timing of birth
Increasing evidence suggests the optimal time for delivery for
the general obstetric population is at 39 weeks of gestation
because after this point the risk of neonatal death does not
fall, but the risk of stillbirth increases.76 A Cochrane
systematic review77 suggests routine induction of labour
55
 Care in pregnancies after stillbirth

Death of a baby

Investigations
e.g. postmortem/placental histopathology,
maternal blood tests

Postnatal/preconception appointment:
Offer services, make plan for pregnancy
Community midwife/
primary care
First point of contact
EPAU

Self-referral Commence appropriate interventions

Other specialist review

Booking appointment/dating scan (11–13 weeks)
if required

Anomaly scan at 20 weeks

Does the mother

accept referral to
Rainbow Clinic?

Yes

Placental scan at 23 weeks

unless specifiic early onset pathology

Phone contact
Glucose tolerance test (if indicated) at 26 weeks
and support

Ultrasound scan as required to monitor growth,

e.g. if abnormal, placental screen fortnightly from
26 weeks of gestation, or if normal, placental
screen 3-weekly from 28 weeks of gestation

Monitor and deliver as Yes Abnormality detected on

indicated by relevant
scanning or screening?
national guidance
No

Plan for birth – offer elective birth from 38 weeks

Figure 1. Pathway for care of women who have a history of stillbirth. Care is initatied from the time of death. Postnatal care is shown in purple
boxes, initial antenatal care is shown in green boxes and care in a dedicated antenatal service is shown in blue boxes. EPAU = early pregnancy
assessment unit.

56 ª 2020 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

(IOL) ‘at term’ would reduce perinatal mortality by 70%. A
population study,78 a systematic review 79 and a recent
randomised trial80,81 demonstrated no increase in caesarean
section rates associated with planned IOL at 39 weeks of
gestation, suggesting that this approach does not increase
harm for women. However, additional emotional care is
required in many women who have previously suffered
stillbirth and induced delivery from 38 weeks of gestation
may be indicated. One observational study from South
Africa82 found that, of 306 women with a history of stillbirth,
203 (66%) had an indication for birth before 39 weeks of
gestation. Of the remaining women, 51% went into
spontaneous labour before the proposed date of induction.
Two-thirds of women in this study required early
intervention with a clear indication – this demonstrates the
importance of specialised antenatal care in a pregnancy
following stillbirth owing to the high-risk nature of the
subsequent pregnancy.
Conclusion
Stillbirth has a devastating effect on parents and their families
and bears increased costs, particularly in subsequent
pregnancies. Advances in understanding the causes of stillbirth
and the potential risk of recurrence will enable management
strategies and possible treatments to be developed for women in
subsequent pregnancies who are at increased risk of stillbirth.
More evidence is required, especially from larger, more robust
studies, to guide practice in these high-risk pregnancies; many
current studies are limited by small participant numbers or
methodological weaknesses. In particular, studies are needed to
determine the origins of the increased risk of placental problems
in subsequent pregnancies and whether this is restricted to
specific causes of stillbirth. Evidence is needed to determine
effective therapies for recurrent placental conditions. Further
research is also needed to discern the optimal method of
supporting families through these medically and emotionally
complex pregnancies. Importantly, stillbirth is an established
risk factor for subsequent adverse outcome. Specialist antenatal
care and increased surveillance throughout pregnancy should be
provided, especially to address the emotional and psychological
effects of previous stillbirth on a woman and her family.
Disclosure of interests
There are no conflicts of interest.
Contribution to authorship
NG and AEPH instigated, researched and wrote the article,
LS wrote the article and created the figure regarding pathway
of care. All authors approved the final version.
ª 2020 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.
Graham et al.
Acknowledgements
The authors would like to thank Mrs Victoria Holmes,
Bereavement Midwife, St Mary’s Hospital, who assisted in the
development of the Rainbow Clinic service.
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