Stillbirth: risk factors and opportunities for
prevention
Vicki Flenady PhD, MMedSc (Clin Epi & Biostats)
Mater Research Institute, University of Queensland
Content
•
•
•
•
Brief overview of global picture
High income country picture – focussing on risk factor
The Lancet’s stillbirth series key recommendations
Stillbirth research initiatives in Australia and New Zealand
Launch April 2011
Australia
London
New York
Geneva
New Delhi
Florence, Italy
Cape Town
All papers can be accessed free at www.lancet.com/series/stillbirth
“These papers, like no other Lancet Series before, have triggered a remarkable
response not just from academia and organisations, but also from the public” The Lancet editors
Global burden of stillbirth
2.65 million
third
trimester
stillbirths
each year
10 countries account for
66% of the world’s
stillbirths – and also 66%
of neonatal deaths and
over 60% of maternal
deaths
1. India
2. Pakistan
3. Nigeria
4. China
5. Bangladesh
6. Dem Rep Congo
7. Ethiopia
8. Indonesia
9. Tanzania
10. Afghanistan
98% of stillbirths occur in low-income and middle-income countries –
Source: Lawn JE, Blencowe H, Pattinson R, et al, for The Lancet’s Stillbirths Series steering committee. Stillbirths: Where? When? Why? How to
make the data count? Lancet 2011;
published
online April
14. thirds
DOI:10.1016/S0140-6736(10)62187-3.
more
than
two
are in rural families.
Stillbirths don’t count …
1. Global data
NOT routinely reported to World Health Organization
NOT included in the Global Burden of Disease metrics
NOT measured appropriately in most national surveys
2. Global goals eg Millennium Development Goals (MDGs)
Stillbirths NOT counted in the MDGs although intimately linked to:
•
Maternal health in MDG 5
•
Neonatal deaths, accounting for 41% of child deaths in MDG4
•
Poverty (MDG 1) and girls’ education (MDG2)
Stillbirths often missed in national or international health policy and
programmes … Yet they count for families
Reality for families
Giovanni Presutti CiaoLapo
Over 7200 families a day experience a
stillbirth late in pregnancy…
In Australia over 2000 stillbirths each year: 7
every day (I in 130 women)
Whether they are famous or not, in a rich
country or poor, the grief is
overwhelming, and usually hidden
Sands UK
Goal by 2020
Countries with a current stillbirth rate of less
than 5 per 1000 births, the goal by 2020 is
to eliminate all preventable stillbirths and
close equity gaps.
PMNCH
Countries with a current stillbirth rate of more
than 5 per 1000 births to reduce their stillbirth
rates by at least 50% from the 2008 rates.
www.thelancet.com/series/stillbirth
Stillbirths during labour – 1.2 million a year
The risk of stillbirth during labour (intrapartum) for an African woman is 50 times
higher than for a woman in the UK/ANZ.
Source: Lawn JE, Blencowe H, Pattinson R, et al, for The Lancet’s Stillbirths Series steering committee. Stillbirths: Where? When? Why? How to
55%
of2011;
allpublished
stillbirths
are14.for
rural families in Africa, South Asia
make the data count?
Lancet
online April
DOI:10.1016/S0140-6736(10)62187-3.
Stalled progress
in high income countries
Stillbirth rates halved 1950-1975 with improvements in infection treatment and obstetric
–The
rates
have
now
stalled
Source: Goldenberg RL, McClure EM, Bhutta ZA,care
et al, for
Lancet’s
Stillbirths
Series
steering committee. Stillbirths: the vision for 2020.
Lancet 2011;
Stillbirths at 28 weeks or more in
high-income settings
Differences between countries and within countries show that more
Source: Flenady V, Middleton P, Smith GC, et al, for The Lancet’s Stillbirths Series steering committee. Stillbirths: the way forward in highreduction
rates is achievable
income countries. Lancet 2011; published
online Aprilin
14.stillbirth
DOI:10.1016/S0140-6736(11)60064-0.
Late gestation (>28weeks) stillbirth rates per 1000 births
of 193 countries (Cousens et al., 2011)
Australia
2.9 (ranked 15)
New Zealand
3.5 (ranked 34)
If Australia and New Zealand achieved the stillbirth
rate of the best performing country, 368 stillbirths
would be avoided each year
Finland
2.0 (ranked 1)
Germany
USA
UK
France
2.4 (ranked 6)
3.0 (ranked 17)
3.5 (ranked 33)
3.9 (ranked 41)
Potentially Modifiable Risk
Factors for Stillbirth in HIC?
Maternal characteristics
• Maternal/ paternal age
• BMI
• Smoking
• Parity
• Ethnicity
• SES & education
Adequacy of antenatal care
Inter-pregnancy interval
Substance use
Alcohol intake
Coffee consumption
Consanguinity
Stress
Medical conditions
• Diabetes
• Hypertensive disease
Pregnancy factors
• Post-term pregnancy
• Multiple pregnancy
• ART conceptions
Pregnancy complications
• FGR & SGA
• Birthweight
Previous stillbirth
Previous caesarean section
Other previous pregnancy
complications
Methodology
Study selection:
Recent, population based studies (1998-Dec 2009)
19,126 studies
reviewed
HIC settings
75 included
Stillbirth definition of ≥20 weeks or ≥ 400 grams
Multivariate analysis controlling for important confounders (i.e. age,
BMI, smoking, medical conditions etc)
Quality appraisal:
Newcastle-Ottawa Scale (NOS) for cohorts and case-controls (Wells GA,
Shea B, O'Connell D, Peterson J, Welch V, Losos M & Tugwell P,
2003).
Data analysis:
Random effect meta-analysis (where appropriate)
Population attributable risk (PAR%)
PAR = Pe (RRe-1) / 1 + Pe (RRe-1)
Maternal age > 35 years
Prevalence 22%
PAR 11%
Prevalence 0.5%
Previous stillbirth
PAR 0.8%
Potentially Modifiable Risk
Factors for Stillbirth in HIC
Maternal overweight & obesity:
BMI 25-30 & >30
PAR 12%: OR 1.23, 1.63 (Prevalence 40%)
(8000 stillbirths each year)
30% of all
stillbirths
Maternal age > 35 years:
PAR 11%, OR 1.65 (Prevalence 22%)
(4000 stillbirths)
Smoking:
PAR 6%; OR 1.36; (Prevalence 17%)
(3000 stillbirths)
Population attributable risk (PAR)
Estimates for maternal demographics
Factor
aOR
95% CI
Prev %
PAR%
Any (<28 wk stillbirth) (single study)
1.8
1.3-2.3
50
17
1 – 3 per week
1.1
1.0- 1.2
>5 per week
1.7
1.0-3.0
Binge
1.5
1.0-2.0
Low socio-economic status (SES)
1.2
1.01-1.4
49.6
9
Low education (<10 or <8yrs)
1.7
1.4-2.0
6.9
5
Illicit drug use
1.9
1.2-3.0
2.4
2
Assisted Reproductive Technology (ART) use
2.7
1.6-4.7
3.1
3
No antenatal care
3.3
3.1-3.6
0.3
1
Caffeine intake >8 cups (SB 20-27 weeks)
2.3
1.3-3.9
Paternal age > 50 years
3.9
1.1-13.8
Alcohol use
Population attributable risk (PAR)
Estimates for medical/pregnancy complications
Factor
aOR
95% CI
Prev %
PAR%
Small for gestational age (SGA) <10%
3.8
2.3-6.3
10.0
23
Placental abruption
18.9
16.9-12.2
1
15
Pre-existing hypertension
2.6
2.1-3.1
4.6
7
Pre-existing diabetes
2.9
2.1-4.1
2.6
5
Pre-eclampsia
1.5
1.1-2.0
5.3
3
Multiple pregnancy (any)
2.9
2.5-3.4
2
3
Pregnancy induced hypertension (PIH)
1.3
1.2-1.6
6.3
2
Multiple pregnancy (twins)
1.6
1.4-1.9
2
1
Pregnancy prolongation (≥42 weeks)
1.3
1.1-1.7
0.9
0.3
Eclampsia
2.2
1.5-3.2
0.1
0.1
Population attributable risk (PAR)
Estimates for previous pregnancy history
Factor
aOR
95% CI
Prev %
PAR%
Primiparity
1.4
1.3-1.5
42
14
Caesarean section
(contentious)
1.3
1.1-1.52
27
7
Stillbirth
2.7
1.6-4.6
0.5
1
SGA + PTB (any)
2.1
1.6-2.8
SGA + PTB 32-36 weeks
3.4
2.1-5.6
SGA+ PTB <32 weeks
5.0
2.5-9.8
SGA + preterm birth (PTB)
Late gestation (>28weeks) stillbirth rates per 1000 births
of 193 countries (Cousens et al., 2011)
Australia
2.9 (ranked 15)
Indigenous
3.5 (ranked 34) Australians
Ranked 56th behind Colombia
and Malaysia
New Zealand
Finland
2.0 (ranked 1)
Germany
USA
UK
France
2.4 (ranked 6)
3.0 (ranked 17)
3.5 (ranked 33)
3.9 (ranked 41)
Indigenous status and stillbirth adjusted analysis
Subgroup analysis: ethnic minorities
PAR%
Risk factor
aOR
AU Indig
PAR %
Smoking (any)
1.7
26%
29%
13%
5%
(14-37)
(16-40)
(6-19)
(3-9)
13%
12%
(9-17)
(9-16)
-
-
Heavy smoking (10+)
1.9
CA Indig
PAR%
US Indig
PAR%
US Afr Am
PAR %
Overweight
1.3
15%
23%
21%
25%
Obesity
1.9
(8-22)
(13-32)
(12-29)
(15-35)
Diabetes
2.9
-
-
-
(3-8)
Hazardous alcohol use
1.7
10%
No antenatal care
3.3
-
8%
5%
(7-8)
(5-6)
5%
(0-24)
8%
(7-9)
Contributory factors and potentially
avoidable perinatal related deaths 2010
Action priorities in high-income countries
− Reduce inequity, intentionally designing policies
and programs to reach underserved women
from poorer communities or ethnic minorities
− Address lifestyle risk factors such as obesity,
smoking, and advanced maternal age
− Improve data quality, Implementation high
quality investigation and perinatal audit linked
to practice change
− Improve detection of pregnancies at increased
risk eg placental dysfunction and fetal growth
restriction
Decreased fetal movements ranked in the top 10 research priorities
Stillbirths by PSANZ PDC,
QLD 2000-2008
Unexplored not explained
Unexplained stillbirth:
possible
13%
Unknown
7%
Congenital abnormality
20%
Hypertension
3%
Unexplained stillbirth:
7%
Maternal conditions
6%
Spontaneous preterm unknown chorio
4%
Specific perinatal
conditions
5%
Spontaneous preterm no chorio
3%
Spontaneous preterm chorio
8%
Perinatal infection
2%
Placenta: Insufficiency
7%
Hypoxic peripartum
death
2%
Placenta: Other
6%
Placenta: APH
7%
ANZ Autopsy rates
Autopsy Rates in Australia and New Zealand
80.00%
Autopsy Rate
70.00%
60.00%
50.00%
40.00%
30.00%
20.00%
10.00%
0.00%
WA
SA
Perinatal Mortality autopsy rate
Stillbirth autopsy rate
Neonatal death autopsy rate
ACT
NZ
TAS
Region
VIC
NSW
QLD
NT
Perinatal Society of Australia and New
Zealand Guidelines
Promoting a systematic approach to clinical
care, including audit, around the time of a
perinatal death.
•
•
•
•
•
•
Institutional Perinatal Mortality Audit
Investigation of stillbirth
Investigation of neonatal death
Autopsy
Perinatal Mortality Classification
Psychological and social aspects of
bereavement care
IMPROVE (IMproving Perinatal Mortality Review &
Outcomes Via Education) Program
Station 1:
Communicating with
parents about
perinatal autopsy
Station 6:
Psychological and
social aspects of
perinatal bereavement
Study Guide
Station 2:
Autopsy and placental
examination
Teaching Stations
Formative Assessment
Station 5:
Audit and
classification of
perinatal death
SCORPIO Methodology: D.A. Hill,
Medical Teacher. 1992; 14: 37-41
Station 4:
Examination of babies
who die in the
perinatal period
Station 3:
Investigation of
perinatal deaths
National Perinatal Death Clinical Audit Tool
On-line: A platform for audit and research
1. Effective online data
collection tool for
maternity hospitals
2. Includes stillbirth and
neonatal deaths
3. Reports automatically
generated for Hospital
and Health Department
reporting of perinatal
deaths
National prospective perinatal death data
collection: Audit and research
30 maternity hospitals
IMPROVE workshops
First study: Stillbirth investigation and
causes;
1,000 stillbirths – causes, contributing
factors, yield of tests, costs
Decreased fetal movements
− Possible adaptive response to placental dysfunction
− DFM is associated with a doubling of the risk of FGR (Flenady 2011)
− Women who reported DFM (and came to hospital with a live
baby) had 4 times the risk of stillbirth compared with women who
did not report DFM (Flenady 2011)
− Women perceiving a reduction in strength of fetal movements had
twice the risk of stillbirth (Stacey 2010)
DFM Reporting and Practice in Australia
and New Zealand
Women:
−
50% wait 24 hours or more to report DFM
− 60% say it is normal for movements to decrease towards term
− 70% indicate awareness of FM would NOT help identify a baby at risk
Obstetricians and Midwives:
− asking women about FM is important
− define DFM most commonly by maternal perception of DFM
− lack of clinical practice guidelines
− For women with DFM :
− Suggest drink some cold/iced water
− Low level of ultrasound scan (< 10%)
Evidence for raising awareness (+/- kick counting)
Cochrane systematic review of Kick
Counting:
INSUFFICIENT EVIDENCE
Grant trial- large Cluster RCT,
methodological flaws
Lowered stillbirth rate after 28 weeks by 30%
DFM Guidelines in Australia and New
Zealand
− All pregnant women should be routinely provided
verbal and written information about normal FM
− All women should be advised to contact their
health care provider if they have any concern
about decreased or absent FM and be advised not
to wait until the next day
− Maternal concern of DFM overrides any other
definition
− Women should be assessed within 12 hours of
reporting DFM; CTG, clinical assessment of fetal
growth, risk factor
− USS if risk factors present or clinical concerns
(managed a high-risk pregnancy)
DFM Information for women
Translations: Korean, Arabic, Spanish, Hindi, Vietnamese, Chinese Simplified & Traditional
My Baby’s Movements Trial
Smartphone Tool
− User-controlled
− Information about fetal
movements and what to expect
as pregnancy progresses
− Incudes daily fetal movement
prompt (time chosen by woman)
− Includes movement monitoring
option if concerned about fetal
movements
− Designed to be supportive and
non-directive, and minimise
unnecessary anxiety and to
respect women’s right to
autonomy
My Baby’s Movements Trial
Primary outcome:
Stillbirth 28 weeks or more
Randomisation:
Assigned to timing of
intervention using computergenerated random number
table
Implementation schedule:
9 time periods of 4 months over
36months with groups of 3-4
hospitals in each group
27 hospitals of 3000 births/year
over a 3 year period
Biophysical and biochemical tests
to predict stillbirth
Low predictive accuracy : fetoplacental proteins, first- and second-trimester
screening for Down syndrome, multivariable prediction models, uterine
artery Doppler velocimetry, nuchal translucency, fetal growth, flow in
ductus venosus, thyroid function-related tests, maternal hemoglobin
levels, and cervicovaginal infection had a low predictive accuracy for
stillbirth
Moderate to high predictive for stillbirth placental conditions: A pulsatility
index in the uterine arteries >90th percentile and low levels of pregnancy
associated plasma protein A (PAPP-A) had a moderate to high predictive
accuracy for stillbirth related to placental abruption, small for gestational
age or preeclampsia
Emerging evidence microRNAs derived from the placenta circulate in the
maternal blood during pregnancy and may serve as non-invasive
biomarkers for pregnancy complications.
Summary
• Maternal overweight and obesity, smoking and advanced age are
important potentially avoidable risk factors
• Primiparity is an important risk factor. With increasing incidence of
combined risk factors – stillbirth rates could increase
• Abruption, Diabetes and Hypertension remain important factors in
stillbirth
• Must improve data quality including clinical audit linked to practice
change
• Research to improve detection of women at risk in the antenatal
period is a priority
Acknowledgements
The Lancet's Stillbirth Series
Steering Committee
J Frederik Frøen, Joy Lawn, Zulfiqar
Bhutta, Robert Pattinson, Vicki Flenady,
Robert Goldenberg, Monir Islam
MBM Trial Investigators
Glenn Gardener, David Ellwood,
Philippa Middleton, Michael Coory,
Caroline Crowther, Christine East, Emily
Callander, Frances Boyle, Adrian
Charles, Adrienne Gordon, Alison Kent,
Belinda Jennings, Deborah Schofield,
Glyn Teale, Jonathan Morris, Kassam
Mahomed, Susan Vlack, Jane Norman,
Fredrik Frøen,
International Collaborators
Ruth Fretts, Fredrik Frøen,
Alex Haezell; Jane Norman
ANZSA Researchers
Aleena Wojcieszek, Annie McArdle, Cate
Nagal, Ann Peacock, Paula Dillon, Debra
Creedy, Jenny Gamble, Jocelyn Toohil,
Tomasina Stacey, Kassam Mahomen, Julie
MacPhail, Glenn Gardener, Yogesh
Chadha, Ibi Ibiebele, Laura Koopmans,
Dom Rossouw, Kristen Gibbons, Peter Gray
Professor Michael Humphrey
Queensland Maternal Perinatal Quality
Council
We also thank the women and clinicians who contributed data
Acknowledgements
Collaborators
ANZSA Consortium hospitals and investigators
QLD: Gold Coast Hospital, Anne Sneddon; Ipswich Hospital, Kassam Mahomed;
Nambour Hospital, Ted Weaver; Caboolture Hospital, Kate Kerridge; Cairns Base
Hospital, Paul Howat; Logan Hospital, Janet Draper; Townville Hospital, David
Watson and Anne-Maree Lawrence; Mater Mother’s Hospital Public, Mater Mother’s
Hospital Private, Glenn Gardener; Royal Women’s Hospital Yogesh Chadha.
NSW: Nepean Hospital, Michael Peek; Royal Prince Alfred Hospital, Sydney; Royal
Hospital for Women, Leo Leader; Royal North Shore Hospital, Jonathan Morris.
VIC: Sunshine Hospital, Glyn Teale;
Mercy Hospital, Robyn Aldridge; Kasey and Dandenong Hospitals, Monash Medical
Centre, Chris East; Royal Women’s Hospital Melbourne, Fiona Cullinane; Mercy
Hospital for Women, Sue Walker.
WA: King Edward Memorial, Adrian Charles and Belinda Jennings.
SA: Women’s and Children’s Hospital, Rodney Petersen.
NZ: Auckland City Hospital, Peter Stone and Nick Waller; Middlemore Hospital, Dr
Graham Parry.
Thank you
Vicki Flenady
vflenady@mmri.mater.org.au