Risk factors for late preterm and term stillbirth: A secondary analysis of an individual participant data meta-analysis.

OBJECTIVE: Identify independent and novel risk factors for late-preterm (28-36 weeks) and term (≥37 weeks) stillbirth and explore development of a risk-prediction model. DESIGN: Secondary analysis of an Individual Participant Data (IPD) meta-analysis investigating modifiable stillbirth risk factors. SETTING: An IPD database from five case-control studies in New Zealand, Australia, the UK and an international online study. POPULATION: Women with late-stillbirth (cases, n = 851), and ongoing singleton pregnancies from 28 weeks' gestation (controls, n = 2257). METHODS: Established and novel risk factors for late-preterm and term stillbirth underwent univariable and multivariable logistic regression modelling with multiple sensitivity analyses. Variables included maternal age, body mass index (BMI), parity, mental health, cigarette smoking, second-hand smoking, antenatal-care utilisation, and detailed fetal movement and sleep variables. MAIN OUTCOME MEASURES: Independent risk factors with adjusted odds ratios (aOR) for late-preterm and term stillbirth. RESULTS: After model building, 575 late-stillbirth cases and 1541 controls from three contributing case-control studies were included. Risk factor estimates from separate multivariable models of late-preterm and term stillbirth were compared. As these were similar, the final model combined all late-stillbirths. The single multivariable model confirmed established demographic risk factors, but additionally showed that fetal movement changes had both increased (decreased frequency) and reduced (hiccoughs, increasing strength, frequency or vigorous fetal movements) aOR of stillbirth. Poor antenatal-care utilisation increased risk while more-than-adequate care was protective. The area-under-the-curve was 0.84 (95% CI 0.82-0.86). CONCLUSIONS: Similarities in risk factors for late-preterm and term stillbirth suggest the same approach for risk-assessment can be applied. Detailed fetal movement assessment and inclusion of antenatal-care utilisation could be valuable in late-stillbirth risk assessment.

'I don't need you to criticise me, I need you to support me'. A qualitative study of women's experiences of and attitudes to smoking cessation during pregnancy.

BACKGROUND: Smoking is associated with health inequalities and is the most important modifiable risk factor for poor outcome in pregnancy. AIM: To explore women's experiences of smoking during pregnancy, examine their attitudes and barriers to smoking cessation, and to discover what support they feel might enable them to have a smoke-free pregnancy in future. METHODS: A qualitative study was conducted with nineteen women in the United Kingdom who had smoked at some stage in pregnancy during the last five years. Data were collected through in-depth telephone interviews between June and August 2021. The interviews were audio-recorded, transcribed verbatim, and thematically analysed. FINDINGS: Four key themes were identified: the complex relationship with smoking, being ready to quit, the need for support and understanding, and ideas to support a smoke free pregnancy. The findings revealed that there were two distinct avenues for enabling the support process: encouraging a readiness to quit through identifying individual context, personalised support, and educational risk perception, and, supporting the process of quitting, and offering a range of options, underpinned by a personalised, non-judgemental approach. CONCLUSION: Smoking in pregnancy is a complex issue resulting from a combination of social, emotional, and physical factors. The findings from this study suggest that a combination of approaches should be made available to enable pregnant women who smoke to select the best options for their individual needs. Irrespective of the practical support offered, there is a need for informed, sensitive, individualised support system that women can identify with.

Associations between consumption of coffee and caffeinated soft drinks and late stillbirth-Findings from the Midland and North of England stillbirth case-control study.

OBJECTIVE: The consumption of caffeinated drinks and soft drinks is widespread in society, including by pregnant women. Data regarding the association of caffeine intake and stillbirth are varied. We aimed to investigate the degree of consumption of caffeinated drinks or soft drinks in the last four weeks of pregnancy in women who experienced a late stillbirth compared to women with ongoing live pregnancies at similar gestation. Influences on maternal caffeine intake and soft drink consumption during pregnancy were also investigated. STUDY DESIGN: A case-control study undertaken in 41 maternity units in the United Kingdom. Cases were women who had a singleton non-anomalous stillbirth ≥28 weeks' gestation (n = 290) and controls were women with an ongoing pregnancy at the time of interview (n = 729). Data were collected using an interviewer-administered questionnaire which included questions regarding consumption of a variety of caffeinated drinks and soft drinks in the last four weeks of pregnancy as well as other behaviours (e.g. cigarette smoking). RESULTS: Multivariable analysis adjusting for co-existing demographic and behavioural factors found the consumption of instant coffee, energy drinks and cola were associated with increased risk of stillbirth. There was an independent association between caffeine intake and late stillbirth (adjusted Odds Ratio 1.27, 95 % Confidence Interval (95 %CI) 1.14, 1.43 for each 100 mg increment/day). 15 % of cases and 8% of controls consumed more than the World Health Organisation (WHO) recommendation (>300 mg of caffeine/day; aOR 2.30, 95 % CI 1.40, 4.24). The population attributable risk for stillbirth associated with >300 mg of caffeine/day was 7.4 %. The majority of respondents reduced caffeine consumption in pregnancy. Midwives and internet resources were the most frequently used sources of information which influenced maternal behaviour with regard to soft drinks and caffeine, and this did not differ between cases and controls. CONCLUSIONS: Women should be informed that consumption of caffeine during pregnancy is associated with increased risk of stillbirth, particularly at levels greater than recommended by the WHO (>300 mg/day). Recommendations from midwives and internet-based resources are likely to be the most effective means to influence maternal behaviour.

Associations between symptoms of sleep-disordered breathing and maternal sleep patterns with late stillbirth: Findings from an individual participant data meta-analysis.

BACKGROUND AND OBJECTIVES: Sleep-disordered breathing (SDB) affects up to one third of women during late pregnancy and is associated with adverse pregnancy outcomes, including hypertension, diabetes, impaired fetal growth, and preterm birth. However, it is unclear if SDB is associated with late stillbirth (≥28 weeks' gestation). The aim of this study was to investigate the relationship between self-reported symptoms of SDB and late stillbirth. METHODS: Data were obtained from five case-control studies (cases 851, controls 2257) from New Zealand (2 studies), Australia, the United Kingdom, and an international study. This was a secondary analysis of an individual participant data meta-analysis that investigated maternal going-to-sleep position and late stillbirth, with a one-stage approach stratified by study and site. Inclusion criteria: singleton, non-anomalous pregnancy, ≥28 weeks' gestation. Sleep data ('any' snoring, habitual snoring ≥3 nights per week, the Berlin Questionnaire [BQ], sleep quality, sleep duration, restless sleep, daytime sleepiness, and daytime naps) were collected by self-report for the month before stillbirth. Multivariable analysis adjusted for known major risk factors for stillbirth, including maternal age, body mass index (BMI kg/m2), ethnicity, parity, education, marital status, pre-existing hypertension and diabetes, smoking, recreational drug use, baby birthweight centile, fetal movement, supine going-to-sleep position, getting up to use the toilet, measures of SDB and maternal sleep patterns significant in univariable analysis (habitual snoring, the BQ, sleep duration, restless sleep, and daytime naps). Registration number: PROSPERO, CRD42017047703. RESULTS: In the last month, a positive BQ (adjusted odds ratio [aOR] 1.44, 95% confidence interval [CI] 1.02-2.04), sleep duration >9 hours (aOR 1.82, 95% CI 1.14-2.90), daily daytime naps (aOR 1.52, 95% CI 1.02-2.28) and restless sleep greater than average (aOR 0.62, 95% CI 0.44-0.88) were independently related to the odds of late stillbirth. 'Any' snoring, habitual snoring, sleep quality, daytime sleepiness, and a positive BQ excluding the BMI criterion, were not associated. CONCLUSION: A positive BQ, long sleep duration >9 hours, and daily daytime naps last month were associated with increased odds of late stillbirth, while sleep that is more restless than average was associated with reduced odds. Pregnant women may be reassured that the commonly reported restless sleep of late pregnancy may be physiological and associated with a reduced risk of late stillbirth.

An Individual Participant Data Meta-analysis of Maternal Going-to-Sleep Position, Interactions with Fetal Vulnerability, and the Risk of Late Stillbirth.

BACKGROUND: Maternal supine going-to-sleep position has been associated with increased risk of late stillbirth (≥ 28 weeks), but it is unknown if the risk differs between right and left side, and if some pregnancies are more vulnerable. METHODS: Systematic searches were undertaken for an individual-level participant data (IPD) meta-analysis of case-control studies, prospective cohort studies and randomised trials undertaken up until 26 Jan, 2018, that reported data on maternal going-to-sleep position and stillbirth. Participant inclusion criteria included gestation ≥ 28 weeks', non-anomalous, singleton pregnancies. The primary outcome was stillbirth. A one-stage approach stratified by study and site was used for the meta-analysis. The interaction between supine going-to-sleep position and fetal vulnerability was assessed by bi-variable regression. The multivariable model was adjusted for a priori confounders. Registration number: PROSPERO, CRD42017047703. FINDINGS: Six case-control studies were identified, with data obtained from five (cases, n = 851; controls, n = 2257). No data was provided by a sixth study (cases, n = 100; controls, n = 200). Supine going-to-sleep position was associated with increased odds of late stillbirth (adjusted odds ratio [aOR] 2.63, 95% CI 1.72-4.04, p < 0.0001) compared with left side. Right side had similar odds to left (aOR 1.04, 95% CI 0.83-1.31, p = 0.75). There were no significant interactions between supine going-to-sleep position and assessed indicators of fetal vulnerability, including small-for-gestational-age infants (p = 0.32), maternal obesity (p = 0.08), and smoking (p = 0.86). The population attributable risk for supine going-to-sleep position was 5.8% (3.2-9.2). INTERPRETATION: This IPD meta-analysis confirms that supine going-to-sleep position is independently associated with late stillbirth. Going-to-sleep on left or right side appears equally safe. No significant interactions with our assessed indicators of fetal vulnerability were identified, therefore, supine going-to-sleep position can be considered a contributing factor for late stillbirth in all pregnancies. This finding could reduce late stillbirth by 5.8% if every pregnant woman ≥ 28 weeks' gestation settled to sleep on her side.

Ethno-Specific Risk Factors for Adverse Pregnancy Outcomes: Findings from the Born in Bradford Cohort Study.

Objectives Preterm birth (PTB) and small for gestational age (SGA) are major causes of perinatal mortality and morbidity. Previous studies indicated a range of risk factors associated with these poor outcomes, including maternal psychosocial and economic wellbeing. This paper will explore a range of psycho-social and economic factors in an ethnically diverse population. Methods The UK's Born in Bradford cohort study recruited pregnant women attending a routine antenatal appointment at 26-28 weeks' gestation at the Bradford Royal Infirmary (2007-2010). This analysis includes 9680 women with singleton live births who completed the baseline questionnaire. Data regarding maternal socio-demographic and mental health were recorded. Outcome data were collected prospectively, and analysed using multivariate regression models. The primary outcomes measured were: PTB (<37 weeks' gestation) and SGA (<10th customised centile). Results After adjustment for socio-demographic and medical factors, financial strain was associated with a 45 % increase in PTB (OR 1.45: 95 % CI 1.06-1.98). Contrary to expectation, maternal distress in Pakistani women was negatively associated with SGA (OR 0.65: CI 0.48-0.88). Obesity in White British women was protective for PTB (OR 0.67: CI 0.45-0.98). Previously recognized risk factors, such as smoking in pregnancy and hypertension, were confirmed. Conclusions This study confirms known risk factors for PTB and SGA, along with a new variable of interest, financial strain. It also reveals a difference in the risk factors between ethnicities. In order to develop appropriate targeted preventative strategies to improve perinatal outcome in disadvantaged groups, a greater understanding of ethno-specific risk factors is required.

The Midland and North of England Stillbirth Study (MiNESS).

BACKGROUND: The United Kingdom has one of the highest rates of stillbirth in Europe, resulting in approximately 4,000 stillbirths every year. Potentially modifiable risk factors for late stillbirths are maternal age, obesity and smoking, but the population attributable risk associated with these risk factors is small.Recently the Auckland Stillbirth Study reported that maternal sleep position was associated with late stillbirth. Women who did not sleep on their left side on the night before the death of the baby had double the risk compared with sleeping on other positions. The population attributable risk was 37%. This novel observation needs to be replicated or refuted. METHODS/DESIGN: Case control study of late singleton stillbirths without congenital abnormality. Controls are women with an ongoing singleton pregnancy, who are randomly selected from participating maternity units booking list of pregnant women, they are allocated a gestation for interview based on the distribution of gestations of stillbirths from the previous 4 years for the unit. The number of controls selected is proportional to the number of stillbirths that occurred at the hospital over the previous 4 years. DATA COLLECTION: Interviewer administered questionnaire and data extracted from medical records. SAMPLE SIZE: 415 cases and 830 controls. This takes into account a 30% non-participation rate, and will detect an OR of 1.5 with a significance level of 0.05 and power of 80% for variables with a prevalence of 57%, such as non-left sleeping position. STATISTICAL ANALYSIS: Mantel-Haenszel odds ratios and unconditional logistic regression to adjust for potential confounders. DISCUSSION: The hypotheses to be tested here are important, biologically plausible and amenable to a public health intervention. Although this case-control study cannot prove causation, there is a striking parallel with research relating to sudden infant death syndrome, where case-control studies identified prone sleeping position as a major modifiable risk factor. Subsequently mothers were advised to sleep babies prone ("Back to Sleep" campaign), which resulted in a dramatic drop in SIDS. This study will provide robust evidence to help determine whether such a public health intervention should be considered. TRIAL REGISTRATION NUMBER: NCT02025530.

Relationship between obesity, ethnicity and risk of late stillbirth: a case control study.

BACKGROUND: In high income countries there has been little improvement in stillbirth rates over the past two decades. Previous studies have indicated an ethnic disparity in the rate of stillbirths. This study aimed to determine whether maternal ethnicity is independently associated with late stillbirth in New Zealand. METHODS: Cases were women with a singleton, late stillbirth (≥ 28 weeks' gestation) without congenital abnormality, born between July 2006 and June 2009 in Auckland, New Zealand. Two controls with ongoing pregnancies were randomly selected at the same gestation at which the stillbirth occurred. Women were interviewed in the first few weeks following stillbirth, or at the equivalent gestation for controls. Detailed demographic data were recorded. The study was powered to detect an odds ratio of 2, with a power of 80% at the 5% level of significance, given a prevalence of the risk factor of 20%. A multivariable regression model was developed which adjusted for known risk factors for stillbirth, as well as significant risk factors identified in the current study, and adjusted odds ratios and 95% confidence intervals were calculated. RESULTS: 155/215 (72%) cases and 310/429 (72%) controls consented. Pacific ethnicity, overweight and obesity, grandmultiparity, not being married, not being in paid work, social deprivation, exposure to tobacco smoke and use of recreational drugs were associated with an increased risk of late stillbirth in univariable analysis. Maternal overweight and obesity, nulliparity, grandmultiparity, not being married and not being in paid work were independently associated with late stillbirth in multivariable analysis, whereas Pacific ethnicity was no longer significant (adjusted Odds Ratio 0.99; 0.51-1.91). CONCLUSIONS: Pacific ethnicity was not found to be an independent risk factor for late stillbirth in this New Zealand study. The disparity in stillbirth rates between Pacific and European women can be attributed to confounding factors such as maternal obesity and high parity.

Fetal growth restriction and other risk factors for stillbirth in a New Zealand setting.

BACKGROUND: Stillbirth affects almost 1% of pregnant women in the Western world but is still not a research priority. AIMS: To assess in a cohort of stillbirths: the demographic risk factors, the prevalence of small for gestational age (SGA) by customised and population centiles, and the classification of death using the Perinatal Society of Australia and New Zealand Perinatal Death Classification (PSANZ-PDC). METHODS: The study population comprised 437 stillborn babies (born from 1993 to 2000 at National Women's Hospital, Auckland, New Zealand) and their mothers. The referent population for demographic factors was live births n=69 173. RESULTS: After multivariable analysis, risk factors for stillbirths were: Indian (odds ratio (OR) 1.85, 95%CI (1.18, 2.91)), or Pacific Islander (OR 1.65, 95%CI (1.27, 2.14)); smoking (OR 1.33, 95%CI (0.99, 1.79)) or unknown smoking status (OR 2.87, 95%CI (2.30, 3.58)); nulliparity (OR 1.42, 95%CI (1.10, 1.83)), and para 2 (OR 1.36, 95%CI (1.01, 1.83)). One hundred and twenty-nine (46%) stillbirths born>or=24 weeks (n=278) were SGA by customised, and 94 (34%) by population centiles. Customised SGA was more common in preterm versus term stillbirths (101 of 198 (51%) vs 28 of 80 (35%), respectively, P=0.02) but rates of population SGA did not differ (72 of 198 (36%) vs 22 of 80 (28%) P=0.16). 'Spontaneous preterm' was the most common cause of stillbirth at <28 weeks and 'unexplained' at >or=28 weeks using PSANZ-PDC classification. CONCLUSIONS: This study again emphasises the importance of suboptimal fetal growth as an important risk factor for stillbirth. Customised centiles identified more stillborn babies as SGA than population centiles especially preterm.