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?