MiNESS: The Midlands and North of England Stillbirth Study

• Sponsor: University of Manchester (Other)
• Overall Status: Completed
• CT.gov ID: NCT02025530
• Collaborator: (none)
• Enrollment: 1,030
• Locations: 4
• Actual Duration (Months): 45
• Patients Per Site: 257.5
• Patients Per Site Per Month: 5.7

Study Details

Study Description

Brief Summary

The United Kingdom has one of the highest rates of stillbirth in Europe, with more than 4,000 stillbirths every year; which equates to more than 11 deaths every day. Furthermore, this rate has changed very little over the last 20 years. This loss of life and the adverse psychological consequences urgently needs addressing.

A recent New Zealand study investigating modifiable factors associated with stillbirth (the Auckland Stillbirth Study) found that mothers who did not go to sleep on their left side had a twofold risk of late stillbirth (≥28 weeks gestation) compared to mothers who did go to sleep on their left side. These novel findings need urgent confirmation.

This proposed study aims to confirm or refute these findings and to ascertain whether a preventative programme should be introduced. This proposed study aims to confirm or refute the findings of the Auckland Stillbirth Study.

Participants will be recruited from maternity units in the Midlands and North of England (led by centres in Liverpool, Manchester, West Yorkshire and Birmingham). 291 women with a singleton late stillbirth without congenital abnormality will be interviewed by research midwives shortly after the birth. A control group of 580 women with ongoing pregnancies will be interviewed at a gestation group matched to that at which stillbirths occurred. These data will determine whether an intervention study should be considered. If there is a causal relationship between maternal sleep position and late stillbirth we estimate that upto 37% of late stillbirths might be prevented.

Condition or Disease	Intervention/Treatment	Phase
Stillbirth	Other: Questionnaire

Detailed Description

The death of an unborn child is a prevalent and tragic public health problem which currently affects millions of families worldwide. Late stillbirth (at or beyond 28 weeks of gestation) is one of the few potentially avoidable maternal and child health problems where the rate of decline in high income countries has slowed in recent decades [1]. The United Kingdom currently has one of the highest rates of stillbirth in Europe, ranking 33rd out of 35 high income countries.

The variations in stillbirth rates between high income countries suggest that it should be possible to make further reductions in late stillbirths. The estimated annual reduction in rates of late stillbirth over recent decades is about 1.1% [1], compared to 2.1% for neonatal death rates, with a resultant increase in the proportion of perinatal deaths (stillbirths plus neonatal deaths) attributable to stillbirth [2]. The Lancet Stillbirth Series [1, 3, 4] has highlighted the silent but prevalent public health problem of stillbirth and together with Sands and the Royal College Of Obstetricians and Gynaecologists has called for research to address these unacceptably high rates.

Current established risk factors for late stillbirth in high income countries include:

advanced maternal age (>35 years) [5], high pre-pregnancy body mass index (BMI) [6], smoking [7], reduced antenatal care attendance [8], low socioeconomic status [8] and small for gestational age (SGA) infants [9]. A meta-analysis of population based studies addressing risk factors for stillbirth found that the three most important modifiable risk factors were overweight and obesity (population attributable risk 818%) advanced maternal age (population attributable risk 68%), and smoking (population attributable risk 47%) [3]. Of these only, cigarette smoking may be realistically addressed after pregnancy has started. There has been limited research investigating the role of novel, modifiable factors which have the potential to advance knowledge and address the important gaps in the field of stillbirth research.

This study aims to explore modifiable risk factors for late stillbirth in the UK and to substantiate the recent identification of a new modifiable risk factor for unexpected late pregnancy stillbirths. In the Auckland Stillbirth Study [10] our New Zealand collaborators discovered an approximately two-fold increase in late stillbirth with non-left sided maternal sleep position on the night before the baby died. In addition, women who did not get up at night and those who slept during the day were also at increased risk of stillbirth. The strength of this primary finding was unanticipated and now maternal sleep position requires urgent, rigorous evaluation in another population. MiNESS aims to address these factors.

This multi-centered case control study will recruit 291 women who have experienced a late (≥28 weeks gestation) matched with 580 women who have a continuing pregnancy at the same gestation (controls). The women will be interviewed by an experienced research midwife and an in depth questionnaire will be completed.

Analysis will be carried out using the standard Mantel-Haenszel odds ratio analysis used in case-control studies. Unconditional logistic regression will be used to adjust for potential confounders and to determine the presence of interactions.

Study Design

• Study Type: Observational
• Actual Enrollment: 1030 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: The Midlands and North of England Stillbirth Study - A Case-Control Study of Modifiable Factors in Late Stillbirth
• Actual Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Mar 31, 2016
• Actual Study Completion Date: Dec 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Cases A structured questionnaire will be administered to women who have experienced a late ≥ 28 weeks gestation stillbirth, who have a singleton pregnancy with no congenital abnormality.	Other: Questionnaire; An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls
Controls A structured questionnaire will be administered to controls. These are women matched to the case group by gestation and unit of birth, who have a normal ongoing singleton pregnancy with no congenital abnormality.	Other: Questionnaire; An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls

Outcome Measures

Primary Outcome Measures

1. Maternal Sleep Practices During Pregnancy [One night prior to questionnaire]

   Self-reported going to sleep position in late pregnancy

Secondary Outcome Measures

1. Maternal Perception of Fetal Activity [Two weeks prior to stillbirth / interview]

   Maternal Perception of Fetal Activity reported via the researcher-administered questionnaire.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria: CASES

• Women who experience a stillbirth ≥28 weeks gestation in a participating unit.

Exclusion Criteria:

• Fetal death prior to 28 weeks gestation.

• Women who's babies have a significant congenital abnormality.

• Women with multiple pregnancy.

• Maternal age below 16 years.

• Women unable to give informed consent.

Inclusion Criteria: CONTROLS

• Women with a normal pregnancy matched to gestation and unit of birth to the cases.

Exclusion Criteria:

• Pregnancy under 28 weeks gestation.

• Women who's babies have a significant congenital abnormality.

• Women with multiple pregnancy.

• Maternal age below 16 years.

• Women unable to give informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Liverpool Women's NHS Foundation Trust	Liverpool	Merseyside	United Kingdom	L8 7SS
2	Birmingham Women's Hospital NHS Foundation Trust	Birmingham	West Midlands	United Kingdom	B15 2TG
3	Mid Yorkshire NHS Trust	Dewsbury	Yorkshire	United Kingdom	WF13 4HS
4	Central Manchester University Hospitals NHS Foundation Trust	Manchester		United Kingdom	M13 9WL

Sponsors and Collaborators

• University of Manchester

Investigators

• Principal Investigator: Tomasina Stacey, Mid Yorkshire NHS Trust
• Principal Investigator: Edwin Mitchell, University of Auckland, New Zealand
• Principal Investigator: Lesley McCowan, University of Auckland, New Zealand
• Principal Investigator: Bill Martin, Birmingham Women's Hospital NHS Foundation Trust
• Principal Investigator: Devender Roberts, Liverpool Women's NHS Foundation Trust

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cnattingius S, Haglund B, Kramer MS. Differences in late fetal death rates in association with determinants of small for gestational age fetuses: population based cohort study. BMJ. 1998 May 16;316(7143):1483-7.
• Cousens S, Blencowe H, Stanton C, Chou D, Ahmed S, Steinhardt L, Creanga AA, Tunçalp O, Balsara ZP, Gupta S, Say L, Lawn JE. National, regional, and worldwide estimates of stillbirth rates in 2009 with trends since 1995: a systematic analysis. Lancet. 2011 Apr 16;377(9774):1319-30. doi: 10.1016/S0140-6736(10)62310-0.
• Flenady V, Koopmans L, Middleton P, Frøen JF, Smith GC, Gibbons K, Coory M, Gordon A, Ellwood D, McIntyre HD, Fretts R, Ezzati M. Major risk factors for stillbirth in high-income countries: a systematic review and meta-analysis. Lancet. 2011 Apr 16;377(9774):1331-40. doi: 10.1016/S0140-6736(10)62233-7. Review.
• Frøen JF, Cacciatore J, McClure EM, Kuti O, Jokhio AH, Islam M, Shiffman J; Lancet's Stillbirths Series steering committee. Stillbirths: why they matter. Lancet. 2011 Apr 16;377(9774):1353-66. doi: 10.1016/S0140-6736(10)62232-5. Review.
• Huang DY, Usher RH, Kramer MS, Yang H, Morin L, Fretts RC. Determinants of unexplained antepartum fetal deaths. Obstet Gynecol. 2000 Feb;95(2):215-21.
• Rajaratnam JK, Marcus JR, Flaxman AD, Wang H, Levin-Rector A, Dwyer L, Costa M, Lopez AD, Murray CJ. Neonatal, postneonatal, childhood, and under-5 mortality for 187 countries, 1970-2010: a systematic analysis of progress towards Millennium Development Goal 4. Lancet. 2010 Jun 5;375(9730):1988-2008. doi: 10.1016/S0140-6736(10)60703-9. Epub 2010 May 27. Erratum in: Lancet. 2010 Aug 28;376(9742):686. Lancet. 2010 Jun 19;375(9732):2142.
• Rasmussen S, Albrechtsen S, Irgens LM, Dalaker K, Maartmann-Moe H, Vlatkovic L, Markestad T. Risk factors for unexplained antepartum fetal death in Norway 1967-1998. Early Hum Dev. 2003 Feb;71(1):39-52.
• Stacey T, Thompson JM, Mitchell EA, Ekeroma AJ, Zuccollo JM, McCowan LM. Association between maternal sleep practices and risk of late stillbirth: a case-control study. BMJ. 2011 Jun 14;342:d3403. doi: 10.1136/bmj.d3403.
• Stephansson O, Dickman PW, Johansson A, Cnattingius S. Maternal weight, pregnancy weight gain, and the risk of antepartum stillbirth. Am J Obstet Gynecol. 2001 Feb;184(3):463-9.
• Wisborg K, Kesmodel U, Henriksen TB, Olsen SF, Secher NJ. Exposure to tobacco smoke in utero and the risk of stillbirth and death in the first year of life. Am J Epidemiol. 2001 Aug 15;154(4):322-7.

• Responsible Party: Dr Alexander Heazell, Senior Clinical Lecturer in Obstetrics, University of Manchester
• ClinicalTrials.gov Identifier: NCT02025530
• Other Study ID Numbers: GN2156
• First Posted: Jan 1, 2014
• Last Update Posted: Oct 11, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by Dr Alexander Heazell, Senior Clinical Lecturer in Obstetrics, University of Manchester: Stillbirth; Modifiable risk factors
• Additional relevant MeSH terms: Stillbirth

Study Results

Participant Flow

Recruitment Details	Participants were recruited between April 2014 and March 2016 from 41 maternity units around the United Kingdom.
Pre-assignment Detail	This was a case-control study, so participants were not assigned to a specific arm/group. 5 cases (women who had a stillbirth) were excluded prior to analysis because the baby was found to have a congenital anomaly at post-mortem examination. One control (women with a live baby at interview) was excluded because she had a stillborn baby.

Arm/Group Title	Cases	Controls
Arm/Group Description	A structured questionnaire was administered to women who have experienced a late ≥ 28 weeks gestation stillbirth, who have a singleton pregnancy with no congenital abnormality. Questionnaire: An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls. Clinical information was obtained from maternal case notes following the interview.	A structured questionnaire was administered to controls. These are women matched to the case group by gestation and unit of birth, who have a normal ongoing singleton pregnancy with no congenital abnormality. Questionnaire: An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls. Clinical information was obtained from maternal case notes following the interview.
Period Title: Overall Study
STARTED	296	734
COMPLETED	291	733
NOT COMPLETED	5	1

Baseline Characteristics

Arm/Group Title	Cases (Stillbirth)	Controls (Live Pregnancy)	Total
Arm/Group Description	A structured questionnaire was administered to women who have experienced a late ≥ 28 weeks gestation stillbirth, who have a singleton pregnancy with no congenital abnormality. Questionnaire: An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls. Clinical information was obtained from maternal case notes following the interview.	A structured questionnaire was administered to controls. These are women matched to the case group by gestation and unit of birth, who have a normal ongoing singleton pregnancy with no congenital abnormality. Questionnaire: An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls. Clinical information was obtained from maternal case notes following the interview.	Total of all reporting groups
Overall Participants	291	733	1024
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.0 (5.9)	30.4 (5.1)	30.3 (5.3)
Sex: Female, Male (Count of Participants)
Female	291 100%	733 100%	1024 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Maternal Sleep Practices During Pregnancy
Description	Self-reported going to sleep position in late pregnancy
Time Frame	One night prior to questionnaire

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cases (Stillbirth)	Controls (Live Pregnancy)
Arm/Group Description	A structured questionnaire was administered to women who have experienced a late ≥ 28 weeks gestation stillbirth, who have a singleton pregnancy with no congenital abnormality. Questionnaire: An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls. Clinical information was obtained from maternal case notes following the interview.	A structured questionnaire was administered to controls. These are women matched to the case group by gestation and unit of birth, who have a normal ongoing singleton pregnancy with no congenital abnormality. Questionnaire: An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls. Clinical information was obtained from maternal case notes following the interview.
Measure Participants	291	733
Left	140 48.1%	383 52.3%
Right	73 25.1%	220 30%
Back	19 6.5%	24 3.3%
Tummy	3 1%	4 0.5%
Propped	9 3.1%	15 2%
Variable	32 11%	76 10.4%
Unknown	15 5.2%	11 1.5%

2. Secondary Outcome

Title	Maternal Perception of Fetal Activity
Description	Maternal Perception of Fetal Activity reported via the researcher-administered questionnaire.
Time Frame	Two weeks prior to stillbirth / interview

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cases (Stillbirth)	Controls (Live Pregnancy)
Arm/Group Description	A structured questionnaire was administered to women who have experienced a late ≥ 28 weeks gestation stillbirth, who have a singleton pregnancy with no congenital abnormality. Questionnaire: An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls. Clinical information was obtained from maternal case notes following the interview.	A structured questionnaire was administered to controls. These are women matched to the case group by gestation and unit of birth, who have a normal ongoing singleton pregnancy with no congenital abnormality. Questionnaire: An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls. Clinical information was obtained from maternal case notes following the interview.
Measure Participants	291	733
In last 2 weeks did movements increase?	37 12.7%	254 34.7%
In last 2 weeks did movements decrease?	86 29.6%	63 8.6%
Movements stayed the same	153 52.6%	397 54.2%
Unsure	15 5.2%	19 2.6%

3. Post-Hoc Outcome

Title	Screening for Gestational Diabetes and Fasting Plasma Glucose
Description	Performance of 75g oral glucose tolerance test and the results of glucose tolerance test in cases and controls
Time Frame	During index pregnancy

Outcome Measure Data

Analysis Population Description

Women were excluded from this analysis if they had pre-existing diabetes. Women should have been screened using oral glucose tolerance test if they had a positive family history, were of South Asian or Black Caribbean ethnicity, had a body mass index ≥ 30 kg/m2, or previous pregnancy effected by GDM or macrosomic (birthweight ≥4.5 kg) birth.

Arm/Group Title	Cases (Stillbirth)	Controls (Live Pregnancy)
Arm/Group Description	A structured questionnaire was administered to women who have experienced a late ≥ 28 weeks gestation stillbirth, who have a singleton pregnancy with no congenital abnormality. Questionnaire: An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls. Clinical information was obtained from maternal case notes following the interview.	A structured questionnaire was administered to controls. These are women matched to the case group by gestation and unit of birth, who have a normal ongoing singleton pregnancy with no congenital abnormality. Questionnaire: An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls. Clinical information was obtained from maternal case notes following the interview.
Measure Participants	283	729
Women screened by Oral Glucose Tolerance Test	94 32.3%	277 37.8%
Proportion Diagnosed with GDM	6 2.1%	30 4.1%

Adverse Events

Time Frame	For the duration of participation in the study (e.g. from recruitment until pregnancy outcome for participants in the control arm). As this was an observational study no SAEs were attributed to completion of the maternal questionnaire.
Adverse Event Reporting Description	Stillbirth was not recorded as an adverse event in the case group because it was an entry criteria for the study.
Arm/Group Title	Cases (Stillbirth)		Controls (Live Pregnancy)
Arm/Group Description	A structured questionnaire was administered to women who have experienced a late ≥ 28 weeks gestation stillbirth, who have a singleton pregnancy with no congenital abnormality. Questionnaire: An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls. Clinical information was obtained from maternal case notes following the interview.		A structured questionnaire was administered to controls. These are women matched to the case group by gestation and unit of birth, who have a normal ongoing singleton pregnancy with no congenital abnormality. Questionnaire: An indepth interview will be carried out and a structured questionnaire will be completed by both cases and controls. Clinical information was obtained from maternal case notes following the interview.
All Cause Mortality
	Cases (Stillbirth)		Controls (Live Pregnancy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/296 (0%)		0/734 (0%)
Serious Adverse Events
	Cases (Stillbirth)		Controls (Live Pregnancy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/296 (0%)		0/734 (0%)
Other (Not Including Serious) Adverse Events
	Cases (Stillbirth)		Controls (Live Pregnancy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/296 (0%)		0/734 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.