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The Midland and North of
England Stillbirth Study
MiNESS
Jayne Budd
Lead Research Midwife
Welcome
The Team Dr Alexander Heazell.- C.I
Dr Tomasina Stacey - P.I Mid Yorks
Dr Bill Martin - P.I Birmingham Womens
Dr Devender Roberts - P.I Liverpool Womens
Professor Ed Mitchell - Auckland
Professor Lesley McCowan - Auckland
A/Prof John Thompson – Auckland
Dr Minglan Li - Auckland
Jayne Budd- Lead Research Midwife
Background
• The UK has one of the highest rates of
stillbirth in Europe, approx 1 in 250
pregnancies end in stillbirth after 28 weeks
gestation (Flenady et al. Lancet, 2011).
• This rate has not declined significantly
despite advances in maternity care.
Data from 1990-2008
Trends in late stillbirth rates in selected high- income
countries, 1990-2008. Flenady et al. Lancet, 2011.
Updated Figures from 2016
Variation in annual rate reduction
since 2000 across 49 countries
• Fastest decline in rates:
Netherlands = 6.8% per annum
• Slowest decline in rates: Slovenia
= +0.5% increase
• UK = 1.4% per annum (lowest third
of rate of decline in HICs)
Flenady et al. Lancet. 2016 Feb 13;387(10019):691-702. Fall Rate
Risk Factors
• Current identified risk factors include: – Advanced maternal age
– Obesity
– Ethnicity
– Cigarette smoking
– Reduced antenatal care attendance
– Low socio-economic status
– Reduced fetal movements
– Small for gestational age
– Previous stillbirth
• Problems – Modest effect size
– Few amenable to modification in pregnancy
Modifiable Risk Factors
Limited health promotion messages
There has been little research investigating
novel, modifiable factors which have the
potential to advance knowledge and
address important gaps in the field of
stillbirth research
Auckland Stillbirth Study
• Aim - To determine whether modifiable risk
factors for late stillbirth could be identified.
• 2006-2009 155 cases and 310 controls were
recruited.
• Hypothesised that sleep disordered breathing &
maternal supine sleep position would be
associated with increased risk of late stillbirth.
Potential mechanism
Maternal cardiac output
Best on left, worst in supine and intermediate on right
side in late pregnancy
Fetal oxygen saturation Changes with maternal position
in labour have similar effect
Cardiac Output
4.8
5
5.2
5.4
5.6
5.8
6
6.2
6.4
6.6
6.8
Left lateral Right lateral Supine
L/m
in
Fetal oxygen saturation
42
44
46
48
50
52
54
Left lateral Right lateral Supine
%
Milsom I, etal Am J Obstet Gynecol 1984;148:764- Carbonne B, et al O+G:1996:88,797
Aortocaval compression:
Anatomy
Grant’s Atlas of Anatomy - JC Boileau Grant 1972
Inferior vena
cava
Aorta
Maternal right Maternal left
Media Interest
Criticism of TASS
• BMJ Editorial –Chappell and Gordon BMJ
2011
• Reporting bias
• Reverse causality
• Recall bias
• More research needed.
Public reaction to TASS
It doesn’t matter
which side I go to
sleep on, I always
turn over in my sleep
& wake up on the
opposite side.
More mother guilt
oh deep joy!
Maybe we should
all just sleep
standing up and
have done with it –
we can’t win!
I wish they wouldn’t publish these research
stories until definitive
research has been done. It
just creates worry & upset.
Having suffered a
stillbirth last
September these
kind of articles
infuriate me.
Articles like this
just add to the
blame even
though the
research is not
that trustworthy
If you are
comfortable
on your back
I wouldn’t worry
The Sydney Stillbirth Study
• Aim - to identify potentially modifiable risk
factors for late pregnancy stillbirth.
• 2006-2011 - 103 cases (after 32 wks) and
192 controls
• Suggests that supine sleep position may
be an additional risk for late stillbirth in an
already compromised fetus.
• (Gordon et al Obstet Gynecol 2015)
Triple Risk Model for Late Stillbirth
Fetal & Placental
Risk Factors
A Stressor Maternal
Risk Factor
Stillbirth
Warland & Mitchell BMC Pregnancy and Childbirth, 2014
Where we want to be….
Where we want to be…
Beginning MiNESS
• Study idea developed 2012
• Application for funding to Cure Kids and Action
Medical Research – awarded 2013
• Study set-up started – September 2013
• First Recruit – April 2014
• Extension funded – September 2015
• Recruitment completed – March 2016
• Study analysis – September 2016 – present
• Papers submitted – April 2017
Aims
• To identify modifiable risk factors for late stillbirth.
• In particular to confirm/ refute the findings regarding maternal sleep factors identified by The Auckland Stillbirth Study (TASS) and Sydney Stillbirth Study
• To clarify the relationship between altered patterns of fetal movements and the risk of stillbirth.
• To explore the interaction between maternal sleep variables, infant factors and risk of late stillbirth.
Hypotheses
• Maternal left sided sleep position reduces the risk of late
stillbirth.
• Supine sleep position increases the risk of late stillbirth
• Increased maternal sleep duration and sleeping during
the day increase the risk of late stillbirth.
• Maternal perception of RFM, prior to fetal death,
increases the risk of late stillbirth.
• There is an interaction between sleep position and
prolonged sleep.
• Non-left sleep position, in conjunction with a
compromised baby increases the risk of late stillbirth.
MiNESS Study Design
A case control study of 291 cases and 582 controls from numerous centres across the
Midlands and the North of England.
Participants will be interviewed face to face and a questionnaire completed.
Published Protocol
Inclusion/ Exclusion criteria
• Case - late stillbirth - on or over 28 week gestation
• Controls – gestation-matched to expectations of stillbirth profile
• Singleton pregnancy.
• No significant congenital abnormality (FASP definition)
• Over 16 years old
• Able to give informed consent
Recruitment
• Cases- recruited from hospital delivery unit
- referral from MW/ Dr
• Controls - randomly selected from booking
list using algorithm
• Researcher-administered questionnaire
Questionnaire
• Demographics
• General health and past history
• Previous pregnancies
• This pregnancy
• Diet
• Personal habits
• Sleep practices
• Fetal movements
• Injury
• Family violence
• Exercise
• Specific questions about when the baby died - for cases.
Progress
Additional Research
• The myths of stillbirth and research
• How do women ACTUALLY feel about
participating in research that investigates
stillbirth?
– Cases
– Controls
Study Results
Unpublished! Confidentiality
agreement
Recruitment to MiNESS
• Recruitment rate
– Cases 45.3%
– Controls 26.2%
• Lower than Auckland Stillbirth Study and the
Sydney Stillbirth Study
– Cases 72% and 67% respectively
– Controls 72% and 84.5% respectively
Participants vs. Non-
participants
• No difference in participation for women of
White, Black or Asian ethnic origin, but women
from other ethnic groups less likely to participate
in cases and controls (OR for other ethnic group
cases 2.63 95%CI 1.69-4.07 compared to
European ethnicity).
• No significant difference in maternal age
between participants and non-participants in the
case group (30.2 vs. 29.6 years, p=0.25); control
participants were significantly older than control
non-participants (30.5 vs. 29.0 years, p<0.0001)
MiNESS Flow Diagram
Gestation
• Median gestation at interview
– Controls 36 w 3 d (IQR) 32 w 6 d - 38 w 5 d)
– Cases 37 w 4 d (IQR 33 w 4 d - 39 w 5)
– p=0.003
• Median time between date of diagnosing
stillbirth and mother presumed date of stillbirth
was 0 days (IQR 0-1).
• Median time between the date of diagnosis of
stillbirth and interview was 25 days (IQR 17-35).
Causes of Stillbirth
ReCoDe Classification Number of
cases
Percentage of cases
A2.2 Acute Infection 13 4.5
A5 Feto-maternal haemorrhage 6 2.1
A7 Fetal Growth Restriction 132 45.2
B1 Umbilical Cord Prolapse 1 0.3
B2 Constricting loop or knot of cord 10 3.4
C1 Placental abruption 19 6.5
C3 Vasa Praevia 1 0.3
C4 Other Placental Insufficiency (inc.
histological evidence)
48 16.4
D1 Chorioamnionitis 6 2.1
E1 Uterine rupture 1 0.3
F1 Diabetes 9 3.1
F6 Obstetric Cholestasis 1 0.3
G1 Intrapartum asphyxia 1 0.3
I1 No relevant condition identified 42 14.4
Demographics
Characteristic Case (n=291) Control (n=733) Total Unadjusted Odds Ratio (95% CI)
Adjusted Odds Ratio (95% CI)
Age (years) <20 7 (2.4) 15 (2.0) 22 (2.2) 1.25 (0.49 to 3.17) 0.61 (0.19 to 1.97) 20-24 48 (16.5) 81 (11.1) 129 (12.6) 1.58 (1.02 to 2.45) 1.49 (0.83 to 2.69) 25-29 82 (28.2) 219 (29.9) 301 (29.4) 1.00 (Reference) 30-34 86 (29.6) 268 (36.6) 354 (34.6) 0.86 (0.60 to 1.22) 1.03 (0.66 to 1.62) 35-39 52 (17.9) 125 (17.1) 177 (17.3) 1.11 (0.74 to 1.68) 1.27 (0.75 to 2.15) 40+ 16 (5.5) 25 (3.4) 41 (4.0) 1.71 (0.87 to 3.36) 1.81 (0.75 to 4.39) Ethnicity White 234 (80.4) 594 (81.0) 828 (80.9) 1.00 (Reference) Black 12 (4.1) 29 (4.0) 41 (4.0) 1.05 (0.53 to 2.09) 1.09 (0.46 to 2.61) Indian 39 (13.4) 95 (13.0) 134 (13.0) 1.04 (0.70 to 1.56) 1.17 (0.65 to 2.18) Others 6 (2.1) 15 (2.0) 21 (2.1) 1.02 (0.39 to 2.65) 1.10 (0.34 to 3.54) Parity 0 167 (57.4) 296 (40.4) 463 (45.2) 2.37 (1.76 to 3.18) 1.67 (1.14 to 2.45) 1-2 92 (31.6) 386 (52.7) 478 (46.7) 1.00 (Reference) 3+ 32 (11.0) 51 (7.0) 83 (8.1) 2.63 (1.60 to 4.33) 2.43 (1.25 to 4.71) Level of Education Graduate Education
99 (34.0) 326 (31.84) 425 (41.5) 1.00 (Reference)
Further Education 112 (38.5) 278 (27.15) 390 (38.1) 1.33 (0.97 to 1.82) 1.17 (0.76 to 1.79)
Secondary education to 16 years
56 (19.2) 100 (9.77) 156 (15.2) 1.84 (1.24 to 2.74) 1.69 (0.96 to 2.98)
No formal educational qualification
23 (7.9) 29 (2.83) 52 (5.1) 2.61 (1.45 to 4.72) 1.33 (0.58 to 3.06)
Demographics
Characteristic Case (n=291) Control (n=733)
Total Unadjusted Odds Ratio (95% CI)
Adjusted Odds Ratio (95% CI)
Body Mass Index Mean 26.91
(15.44- 47.87) Mean 26.02 (15.41-48.59)
Mean 26.27 (15.41- 48.59)
- 1.02 (0.99 to 1.05)
Marital Status Married 149 (51.2) 440 (60.0) 589 (57.5) 1.00 (Reference) Cohabiting 102 (35.1) 222 (30.3) 324 (31.6) 1.36 (1.01 to 1.83) 0.91 (0.59 to 1.40) Single 40 (13.7) 71 (9.7) 111 (10.8) 1.66 (1.08 to 2.56) 1.11 (0.59 to 2.08) Smoking in pregnancy Non Smoking 207 (71.1) 606 (82.7) 813 (79.4) 1.00 (Reference) Smoking 84 (28.9) 127 (17.3) 211 (20.6) 1.94 (1.41 to 2.66) 1.23 (0.76 to 1.99) Birthweight centile <10 134 (46.0) 101 (13.8) 235 (23.0) 7.01 (4.66 to 10.53) 6.22 (3.79 to 10.23) 10-49.99 100 (34.3) 335 (45.7) 435 (42.5) 1.58 (1.07 to 2.32) 1.62 (1.04 to 2.53) 50-89.99 46 (15.8) 243 (33.2) 289 (28.2) 1.00 (Reference) 90+ 10 (3.4) 51 (7.0) 61 (6.0) 1.04 (0.49 to 2.19) 0.76 (0.31 to 1.89)
Sleep position – last night
Sleep duration last night <5.49 129 (44.3) 227 (31.0) 356 (34.8) 1.94 (1.44 to 2.61) 1.83 (1.24 to 2.68) 5.5-8.49 121 (41.6) 413 (56.3) 534 (52.2) 1.00 (Reference) 8.5-9.49 20 (6.9) 55 (7.5) 75 (7.3) 1.24 (0.72 to 2.15) 1.04 (0.52 to 2.07) 9.5+ 19 (6.5) 36 (4.9) 55 (5.4) 1.80 (1.00 to 3.26) 1.49 (0.72 to 3.08) Number of times up to toilet last night 1.0 91 (31.3) 120 (16.4) 211 (20.6) 2.34 (1.70 to 3.21) 2.81 (1.85 to 4.26) 2.1+ 199 (68.4) 613 (83.6) 812 (79.3) 1.00 (Reference) Maternal Daytime naps in last 4 weeks Never 58 (19.9) 157 (21.4) 215 (21.0) 1.00 (Reference) Occasionally 49 (16.8) 153 (20.9) 202 (19.7) 0.87 (0.56 to 1.35) 0.95 (0.54 to 1.66) 1-2 per week 47 (16.1) 180 (24.6) 227 (22.2) 0.71 (0.46 to 1.10) 0.65 (0.38 to 1.13) 3-4 per week 44 (15.1) 110 (15.0) 154 (15.0) 1.08 (0.68 to 1.72) 1.48 (0.83 to 2.64) 5-6 per week 22 (7.6) 39 (5.3) 61 (6.0) 1.53 (0.84 to 2.79) 1.64 (0.77 to 3.47) Everyday 71 (24.4) 93 (12.7) 164 (16.0) 2.07 (1.34 to 3.18) 2.22 (1.26 to 3.94) Unknown 0 (0.0) 1 (0.1) 1 (0.1) - - Maternal going-to-sleep position last night (before stillbirth / interview) Left 140 (48.1) 383 (53.3) 523 (51.1) 1.00 (Reference) Right 73 (25.1) 220 (30.0) 293 (28.6) 0.91 (0.65 to 1.26) 0.67 (0.44 to 1.02) Back 19 (6.5) 24 (3.3) 43 (4.2) 2.17 (1.15 to 4.08) 2.31 (1.04 to 5.11) Tummy 3 (1.0) 4 (0.5) 7 (0.7) 2.05 (0.45 to 9.28) 1.01 (0.13 to 7.81) Propped 9 (3.1) 15 (2.0) 24 (2.3) 1.64 (0.70 to 3.84) 0.44 (0.13 to 1.49) Variable 32 (11.0) 76 (10.4) 108 (10.6) 1.15 (0.73 to 1.82) 0.93 (0.51 to 1.69) Unknown 15 (5.2) 11 (1.5) 26 (2.5) 3.73 (1.67 to 8.32) 3.33 (1.13 to 9.84)
Sleep position – last 4 weeks
Maternal going-to-sleep position in last 4 weeks Left 136 (46.7) 356 (48.6) 492 (48.1) 1.00 (Reference)
Right 75 (25.8) 189 (25.8) 264 (25.8) 1.04 (0.75 to 1.45) Back 16 (5.5) 29 (4.0) 45 (4.4) 1.44 (0.76 to 2.74)
Tummy 2 (0.7) 5 (0.7) 7 (0.7) 1.05 (0.20 to 5.46) Propped 3 (1.0) 8 (1.1) 11 (1.1) 0.98 (0.26 to 3.76) Variable 59 (20.3) 143 (19.5) 202 (19.7) 1.08 (0.75 to 1.55)
Unknown 0 (0.0) 3 (0.4) 3 (0.3) - Maternal sleep position before pregnancy
Left 73 (25.1) 139 (47.8) 212 (20.7) 1.00 (Reference) Right 64 (22.0) 126 (43.3) 190 (18.6) 0.97 (0.64 to 1.46) Back 34 (11.7) 74 (10.1) 108 (10.6) 0.88 (0.53 to 1.44)
Tummy 67 (23.0) 272 (37.1) 339 (33.1) 0.47 (0.32 to 0.69) Propped 1 (0.3) 0 (0.0) 1 (0.1) - Variable 51 (17.5) 117 (16.0) 168 (16.5) 0.83 (0.54 to 1.28)
Unknown 1 (0.3) 5 (0.7) 6 (0.6) 0.38 (0.04 to 3.32)
Population Attributable Risk
Risk Factor Population
exposed
OR PAR 95% CI
Small for Gestational Age 13.8% 7 45.3% 33.6% 56.8%
Nulliparous 40.4% 2.37 35.6% 23.5% 46.8%
3+ parity 7.0% 2.63 10.2% 4.0% 18.9%
Smoking during pregnancy 17.3% 1.94 14.0% 22.3% 37.1%
Obesity 19.5% 1.7 12.0% 3.8% 21.5%
Overweight 29.5% 1.3 8.1% -1.5% 19.5%
No educational
qualifications
4.0% 2.61 6.1% 1.8% 13.0%
Supine going to sleep
position
3.3% 2.17 3.7% 0.5% 9.2%
Comparison with published data
Study Univariate OR for
supine sleep
Multivariate OR for
supine sleep
Auckland 2011 3.28 (1.46 - 7.34) 2.54 (1.04 - 6.18)
Sydney 2015 6.26 (1.2 - 34)
MCSS 2017 3.63 (1.87 - 7.04) 3.67 (1.74 - 7.78)
MiNESS 2017 2.17 (1.15 - 4.08) 2.31 (1.04 - 5.11)
Conclusion
• Maternal supine going-to-sleep position is
associated with increased risk of late stillbirth in
a UK setting.
• This effect has now been demonstrated
consistently by four published studies in
populations comprising different ethnicities and
geographical settings.
• Should we develop recommendations that
women in the third trimester do not settle to
sleep in the supine position?