Clinical trial NCT02025530: The Midlands and North of England Stillbirth Study
Official title: The Midlands and North of England Stillbirth Study - A Case-Control Study of Modifiable Factors in Late Stillbirth
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stillbirth
Keywords: Stillbirth
Modifiable risk factors
Lead sponsor: University of Manchester
Sponsor class: OTHER
First posted: 2014-01-01
Enrollment: 1030
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The sample will be recruited from maternity units in the Midlands and the North of England.

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maternal Sleep Practices During Pregnancy
timeFrame: One night prior to questionnaire
Secondary outcomes:
measure: Maternal Perception of Fetal Activity
timeFrame: Two weeks prior to stillbirth / interview
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: Liverpool Women's NHS Foundation Trust
state: Merseyside
city: Birmingham
country: United Kingdom
facility: Birmingham Women's Hospital NHS Foundation Trust
state: West Midlands
city: Dewsbury
country: United Kingdom
facility: Mid Yorkshire NHS Trust
state: Yorkshire
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals NHS Foundation Trust
Study officials:
affiliation: Mid Yorkshire NHS Trust
name: Tomasina Stacey
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Auckland, New Zealand
name: Edwin Mitchell
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Auckland, New Zealand
name: Lesley McCowan
role: PRINCIPAL_INVESTIGATOR
affiliation: Birmingham Women's Hospital NHS Foundation Trust
name: Bill Martin
role: PRINCIPAL_INVESTIGATOR
affiliation: Liverpool Women's NHS Foundation Trust
name: Devender Roberts
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cousens S, Blencowe H, Stanton C, Chou D, Ahmed S, Steinhardt L, Creanga AA, Tuncalp 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.
citation: 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.
citation: Flenady V, Koopmans L, Middleton P, Froen 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.
citation: Froen 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.
citation: 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. doi: 10.1016/s0378-3782(02)00111-1.
citation: 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. doi: 10.1067/mob.2001.109591.
citation: 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. doi: 10.1093/aje/154.4.322.
citation: 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. doi: 10.1016/s0029-7844(99)00536-0.
citation: 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. doi: 10.1136/bmj.316.7143.1483.
citation: 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.
citation: Budd J, Stacey T, Martin B, Roberts D, Heazell AEP. Women's experiences of being invited to participate in a case-control study of stillbirth - findings from the Midlands and North of England Stillbirth Study. BMC Pregnancy Childbirth. 2018 Aug 6;18(1):317. doi: 10.1186/s12884-018-1956-1.
citation: Heazell AEP, Budd J, Li M, Cronin R, Bradford B, McCowan LME, Mitchell EA, Stacey T, Martin B, Roberts D, Thompson JMD. Alterations in maternally perceived fetal movement and their association with late stillbirth: findings from the Midland and North of England stillbirth case-control study. BMJ Open. 2018 Jul 6;8(7):e020031. doi: 10.1136/bmjopen-2017-020031.
citation: Platts J, Mitchell EA, Stacey T, Martin BL, Roberts D, McCowan L, Heazell AE. The Midland and North of England Stillbirth Study (MiNESS). BMC Pregnancy Childbirth. 2014 May 21;14:171. doi: 10.1186/1471-2393-14-171.