Stillbirth: risk factors and opportunities for prevention PowerPoint Presentation

Stillbirth: risk factors and opportunities for prevention PowerPoint Presentation

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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. ID: 412085

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Presentations text content in Stillbirth: risk factors and opportunities for prevention

Slide1

Stillbirth: risk factors and opportunities for prevention

Vicki Flenady PhD, MMedSc (Clin Epi & Biostats)Mater Research Institute, University of Queensland

Slide2

Content

Brief overview of global picture High income country picture – focussing on risk factorThe Lancet’s stillbirth series key recommendationsStillbirth research initiatives in Australia and New Zealand

Slide3

Launch April 2011

AustraliaLondonNew YorkGenevaNew DelhiFlorence, ItalyCape Town

“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

All papers can be accessed free at

www.lancet.com/series/stillbirth

Slide4

Global burden of stillbirth

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. DOI:10.1016/S0140-6736(10)62187-3.

10 countries account for 66% of the world’s stillbirths – and also 66% of neonatal deaths and over 60% of maternal deaths  1. India2. Pakistan3. Nigeria 4. China5. Bangladesh6. Dem Rep Congo7. Ethiopia8. Indonesia9. Tanzania10. Afghanistan

2.65 million third trimester stillbirths each year

98% of stillbirths occur in low-income and middle-income countries – more than two thirds are in rural families.

Slide5

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 5Neonatal deaths, accounting for 41% of child deaths in MDG4Poverty (MDG 1) and girls’ education (MDG2)

Stillbirths often missed in national or international health policy and programmes … Yet they count for families

Slide6

Reality for families

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

Giovanni Presutti CiaoLapo

Slide7

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. 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

PMNCH

Sands UK

Slide8

Stillbirths during labour – 1.2 million a year

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. DOI:10.1016/S0140-6736(10)62187-3.

The risk of stillbirth during

labour

(

intrapartum

) for an African woman is 50 times higher than for a woman in the UK/ANZ.

55% of all stillbirths are for rural families in Africa, South Asia

Slide9

Stalled progress in high income countries

Source: Goldenberg RL, McClure EM, Bhutta ZA, et al, for The Lancet’s Stillbirths Series steering committee. Stillbirths: the vision for 2020. Lancet 2011;published online April 14. DOI:10.1016/S0140-6736(10)62235-0.

Stillbirth rates halved 1950-1975 with improvements in infection treatment and obstetric care – rates have now stalled

Slide10

Stillbirths at 28 weeks or more in high-income settings

Source: Flenady V, Middleton P, Smith GC, et al, for The Lancet’s Stillbirths Series steering committee. Stillbirths: the way forward in high-income countries. Lancet 2011; published online April 14. DOI:10.1016/S0140-6736(11)60064-0.

Differences between countries and within countries show that more reduction in stillbirth rates is achievable

Slide11

Late gestation (>28weeks) stillbirth rates per 1000 births of 193 countries

(

Cousens et al., 2011)Finland 2.0 (ranked 1)Germany 2.4 (ranked 6)USA 3.0 (ranked 17)UK 3.5 (ranked 33)France 3.9 (ranked 41)

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

Slide12

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 intakeCoffee consumption ConsanguinityStress

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

Slide13

Methodology

Study selection:Recent, population based studies (1998-Dec 2009) HIC settingsStillbirth definition of ≥20 weeks or ≥ 400 gramsMultivariate 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)

19,126 studies reviewed

75 included

Slide14

Maternal age > 35 years

PAR 11%

Prevalence 22%

Slide15

P

revious stillbirth

PAR

0.8%

Prevalence 0.5%

Slide16

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) Maternal age > 35 years: PAR 11%, OR 1.65 (Prevalence 22%) (4000 stillbirths)Smoking: PAR 6%; OR 1.36; (Prevalence 17%) (3000 stillbirths)

30% of all stillbirths

Slide17

Population attributable risk (PAR)

Estimates for maternal demographics

Factor

aOR

95% CI

Prev

%

PAR%

Alcohol

use

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

Slide18

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 (t

wins)

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

Slide19

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

+ preterm birth (PTB)

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

Slide20

Late gestation (>28weeks) stillbirth rates per 1000 births of 193 countries (Cousens et al., 2011)Finland 2.0 (ranked 1)Germany 2.4 (ranked 6)USA 3.0 (ranked 17)UK 3.5 (ranked 33)France 3.9 (ranked 41)

Australia 2.9 (ranked 15)

New Zealand 3.5 (ranked 34)

Indigenous Australians

Ranked 56

th

behind Colombia and Malaysia

Slide21

Indigenous status and stillbirth adjusted analysis

Slide22

Subgroup analysis: ethnic minorities

PAR%Risk factoraOR AU IndigPAR %CA IndigPAR%US IndigPAR%US Afr AmPAR %Smoking (any)1.726%(14-37)29%(16-40)13%(6-19)5%(3-9) Heavy smoking (10+)1.913%(9-17)12%(9-16)--Overweight1.315%(8-22)23%(13-32)21%(12-29)25%(15-35)Obesity1.9Diabetes2.9---5%(3-8)Hazardous alcohol use1.710%(0-24)No antenatal care3.38%(7-9)-8%(7-8)5%(5-6)

Slide23

Contributory factors and potentially avoidable perinatal related deaths 2010

Slide24

Action priorities in high-income countries

Reduce inequity, intentionally designing policies and programs to reach underserved women from poorer communities or ethnic minoritiesAddress lifestyle risk factors such as obesity, smoking, and advanced maternal ageImprove data quality, Implementation high quality investigation and perinatal audit linked to practice changeImprove detection of pregnancies at increased risk eg placental dysfunction and fetal growth restriction

Decreased

fetal movements ranked in the top 10 research priorities

Slide25

Stillbirths by PSANZ PDC, QLD 2000-2008

Slide26

Unexplored not explained

Slide27

ANZ Autopsy rates

Slide28

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 AuditInvestigation of stillbirthInvestigation of neonatal death AutopsyPerinatal Mortality Classification Psychological and social aspects of bereavement care

Slide29

SCORPIO Methodology: D.A. Hill, Medical Teacher. 1992; 14: 37-41

IMPROVE (

IMproving Perinatal Mortality Review & Outcomes Via Education) Program

Study Guide

Teaching Stations

Formative Assessment

Slide30

National Perinatal Death Clinical Audit Tool

On-line: A platform for audit and research

Effective online data collection tool for maternity hospitalsIncludes stillbirth and neonatal deaths Reports automatically generated for Hospital and Health Department reporting of perinatal deaths

Slide31

National prospective perinatal death data collection: Audit and research

First study:

Stillbirth investigation and causes

;

1,000 stillbirths – causes, contributing factors, yield of tests, costs

30 maternity hospitals

IMPROVE workshops

Slide32

Decreased fetal movements

Possible adaptive response to placental dysfunctionDFM 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)

Slide33

Women: 50% wait 24 hours or more to report DFM 60% say it is normal for movements to decrease towards term70% indicate awareness of FM would NOT help identify a baby at riskObstetricians and Midwives:asking women about FM is importantdefine DFM most commonly by maternal perception of DFM lack of clinical practice guidelinesFor women with DFM : Suggest drink some cold/iced water Low level of ultrasound scan (< 10%)

DFM Reporting and Practice in Australia and New Zealand

Slide34

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%

Slide35

DFM Guidelines in Australia and New Zealand

All pregnant women should be routinely provided verbal and written information about normal FMAll 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 factorUSS if risk factors present or clinical concerns (managed a high-risk pregnancy)

Slide36

DFM Information for women

Translations: Korean, Arabic, Spanish, Hindi, Vietnamese, Chinese Simplified & Traditional

Slide37

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

D

esigned

to be supportive and non-directive, and minimise unnecessary

anxiety and to

respect women’s right to autonomy

Slide38

My Baby’s Movements Trial

Primary outcome:Stillbirth 28 weeks or more Randomisation: Assigned to timing of intervention using computer-generated random number tableImplementation 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

Slide39

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

.

Slide40

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

Slide41

Acknowledgements

The Lancet's Stillbirth Series Steering CommitteeJ Frederik Frøen, Joy Lawn, Zulfiqar Bhutta, Robert Pattinson, Vicki Flenady, Robert Goldenberg, Monir Islam

ANZSA ResearchersAleena 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 GrayProfessor Michael HumphreyQueensland Maternal Perinatal Quality Council

International Collaborators Ruth Fretts, Fredrik Frøen, Alex Haezell; Jane Norman

We also thank the women and clinicians who contributed data

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

,

Slide42

Acknowledgements

Slide43

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.

Slide44

Thank you

Vicki Flenady

vflenady@mmri.mater.org.au

Slide45

Slide46

Slide47


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