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

Robin S Cronin; Jessica Wilson; Adrienne Gordon; Minglan Li; Vicki M Culling; Camille H Raynes-Greenow; Alexander E P Heazell; Tomasina Stacey; Lisa M Askie; Edwin A Mitchell; John M D Thompson; Lesley M E McCowan; Louise M O’Brien

doi:10.1371/journal.pone.0230861

. 2020 Mar 26;15(3):e0230861. doi: 10.1371/journal.pone.0230861

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

Robin S Cronin ^1,^*, Jessica Wilson ¹, Adrienne Gordon ², Minglan Li ¹, Vicki M Culling ¹, Camille H Raynes-Greenow ³, Alexander E P Heazell ⁴, Tomasina Stacey ⁵, Lisa M Askie ⁶, Edwin A Mitchell ¹, John M D Thompson ¹, Lesley M E McCowan ¹, Louise M O’Brien ⁷

Editor: Claudio Liguori⁸

¹Departments of Obstetrics and Gynaecology, and Paediatrics: Child and Youth Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

²Discipline of Obstetrics, Gynaecology and Neonatology, University of Sydney, Sydney, Australia

³Sydney School of Public Health, University of Sydney, Sydney, Australia

⁴Division of Developmental Biology & Medicine, Maternal and Fetal Health Research Centre, School of Medical Sciences, University of Manchester, Manchester, England, United Kingdom

⁵Department of Nursing and Midwifery, School of Human and Health Sciences, University of Huddersfield, Huddersfield, England, United Kingdom

⁶National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia

⁷Departments of Neurology Sleep Disorders Center, and Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, United States of America

⁸University of Rome Tor Vergata, ITALY

Competing Interests: Associate Professor O’Brien reports grants from ResMed outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

^✉

* E-mail: r.cronin@auckland.ac.nz, robincronin@xtra.co.nz

Roles

Robin S Cronin: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Writing – original draft, Writing – review & editing

Jessica Wilson: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Writing – review & editing

Adrienne Gordon: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Writing – review & editing

Minglan Li: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Writing – review & editing

Vicki M Culling: Conceptualization, Funding acquisition, Writing – review & editing

Camille H Raynes-Greenow: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Writing – review & editing

Alexander E P Heazell: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Writing – review & editing

Tomasina Stacey: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Writing – review & editing

Lisa M Askie: Conceptualization, Methodology, Writing – review & editing

Edwin A Mitchell: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Writing – review & editing

John M D Thompson: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Writing – review & editing

Lesley M E McCowan: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – review & editing

Louise M O’Brien: Conceptualization, Data curation, Investigation, Methodology, Supervision, Writing – review & editing

Claudio Liguori: Editor

PMCID: PMC7098581 PMID: 32214393

Abstract

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.

Introduction

The loss of a baby from stillbirth has detrimental consequences for the family and the community [1]. The causes of many stillbirths are unexplained [2, 3]. Sleep-disordered breathing (SDB), ranging from snoring to obstructive sleep apnoea (OSA), is common during pregnancy. The cardinal symptom, habitual snoring ≥3 nights per week, affects up to 35% of women in the third trimester [4, 5], and up to 85% of women with pre-eclampsia [6], while objective measures of OSA are estimated to affect between 8% and 26% of pregnant women [7, 8]. SDB is a risk factor for adverse pregnancy outcomes, including gestational hypertension and pre-eclampsia [4, 9, 10], hyperglycaemia [11–13], impaired fetal growth [14–19], and early-term and/or preterm birth [9, 14, 20–22]. SDB is exacerbated by obesity, advanced gestation, and the supine sleep position [23], all of which are themselves associated with an increased risk of late stillbirth [24]. Therefore, pregnant women with SDB may have an increased risk of late stillbirth (≥28 weeks’ gestation) and this risk may be magnified if women settle to sleep supine, however the data is lacking.

Importantly, the association between SDB and maternal sleep patterns (sleep quality, sleep duration, restless sleep, daytime sleepiness, and daytime naps) with late stillbirth is inconsistent across studies. A meta-analysis [25], which included the comparison of stillbirth in women with and without SDB as an outcome measure, using subjective (self-reported snoring) [26, 27] and objective (OSA) [9, 28, 29] measurements, reported no association between SDB and stillbirth. The relationship between sleep duration and late stillbirth was reported in several case-control [26, 30–32] and cross sectional studies [33], however, the results are not consistent in identifying an association. Subjective sleep quality was also not associated with stillbirth in a cross-sectional [33] and case-control [32] study. Other case-control studies [26, 30] reported that daily naps, compared to no naps, were independently associated with late stillbirth. These inconsistencies may be due to differing measurements of these aspects of maternal sleep between studies, or because some studies did not adjust for potential confounders (such as maternal body mass index [BMI kg/m2] and maternal age). Furthermore, as late stillbirth is a relatively rare event, ranging from 1·3 to 8·8/1000 births in high-income countries [3], individual studies have been underpowered to investigate interactions between supine going-to-sleep position and late stillbirth in women with SDB compared to those without.

The triple risk model [34] suggests that late stillbirth may be the culmination of an interplay between stressors (e.g. SDB, supine going-to-sleep position), maternal risk factors (e.g. obesity, age), and fetal-placental vulnerability (e.g. impaired fetal growth, placental dysfunction). Exploration of possible biological pathways [35] of the association of adverse pregnancy outcomes related to SDB suggests that there are multifactorial mechanisms, including sympathetic activation, oxidative stress, inflammation, and endothelial dysfunction, which contribute to maternal cardiovascular dysfunction, metabolic derangement, placental dysfunction, and fetal compromise. Thus, it is plausible that when a mother is in the supine position in late pregnancy and there is reduced maternal-fetal blood flow from aortocaval compression [36, 37], the addition of partial airway collapse with SDB may exacerbate fetal compromise in a vulnerable fetus.

Since SDB and maternal sleep patterns are potentially modifiable during pregnancy (such as lateral position for supine-dependent snoring, continuous positive airway pressure for OSA, and frequency of daytime naps), it is possible that screening and management of these aspects of maternal sleep during pregnancy may support reduction in the rate of late stillbirth. However, there is a need to assess the current evidence from individual studies that have collected data on maternal sleep and stillbirth to determine if they are associated with late stillbirth.

We established the Collaborative Individual Participant Data (IPD) Meta-analysis of Sleep and Stillbirth (CRIBSS) group to address if maternal going-to-sleep position was associated with late stillbirth. This included pre-specified secondary questions on symptoms of SDB and maternal sleep patterns [38], including 1) is SDB associated with late stillbirth, and 2) is supine going-to-sleep position associated with greater risk of late stillbirth in women with SDB compared to those without?

Materials and methods

The study population comprised cases with late stillbirth and controls with ongoing pregnancies from the CRIBSS data. This IPD meta-analysis was registered with the PROSPERO register of systematic reviews (CRD42017047703) and followed the IPD meta-analysis protocol [38], search strategy [24], risk of bias for non-randomised studies (ROBINS-E) tool [39], and published results [24]. Five international case-control studies [26, 27, 30–32] that collected maternal going-to-sleep position and late stillbirth data were included in this pooled IPD meta-analysis.

Participant level inclusion criteria were singleton, non-anomalous pregnancy, ≥28 weeks’ gestation. Exclusion criteria were multiple pregnancy, major congenital abnormality, gestation <28 weeks’ when pregnancy sleep data was collected, termination of pregnancy at ≥28 weeks’, and receiving an intervention that may have affected going-to-sleep position. Maternal sleep data were collected by self-report via face-to-face interview [26, 27, 30, 31] or online survey [32] within six weeks after stillbirth in cases or at a matched gestation in controls.

Late stillbirth, using the international definition of stillbirth [40], “a baby born with no signs of life at or after 28 weeks’ gestation,” was the primary outcome. The analysis included intrapartum stillbirth, with the rationale that the exact time of the stillbirth may be uncertain and that SDB may result in a vulnerable baby that is unable to tolerate labour.

Data analysis

This was a prespecified secondary analysis of an IPD meta-analysis that investigated maternal going-to-sleep position and late stillbirth, with a one-stage approach stratified by study and site. A detailed statistical analysis plan, prior to the analysis, has been published.²⁵ Prespecified potential covariates were: maternal age, earliest pregnancy BMI, ethnicity, parity, education level, marital status, pre-existing hypertension or diabetes, smoking, recreational drug use, supine going-to-sleep position, fetal movements, infant birthweight by customised centiles, and measures of SDB and sleep patterns (‘any’ snoring, habitual snoring, the Berlin Questionnaire [BQ], Epworth Sleepiness Scale [ESS], sleep quality, sleep restlessness, and sleep duration). Frequency of getting up to use the toilet and daytime naps were also included as these are previously reported [26, 30–32] independent risk factors for late stillbirth. Where data exists for multiple time frames, only data for the month prior to the stillbirth were used in the analysis. In cases where the last month data were not available, data collected for the ‘last week’ [31] were used.

There are currently no validated tools for SDB screening during pregnancy, therefore we investigated habitual snoring, a positive BQ [41], and daytime sleepiness using the ESS [42] as proxy indicators. The BQ [41] was developed to identify individuals at risk of OSA in non-pregnant primary care populations and has three categories 1) snoring frequency, loudness, and witnessed apnoea, 2) daytime sleepiness, and 3) BMI >30 and hypertension, with a positive BQ requiring two positive categories. The ESS [42] is a subjective measure of daytime sleepiness with eight questions about the likelihood of dozing off in specified situations, ranging from unlikely (in a car stopped for a few minutes in traffic) to highly likely (lying down to rest in the afternoon). The ESS is coded as 0 = never doze, 1 = slight chance, 2 = moderate chance, and 3 = high chance, with a positive ESS screen indicating clinical levels of daytime sleepiness defined as ≥10.

Data on the usual duration of overnight sleep were also collected. The reference for sleep duration was defined as 6 to 9 hours, with duration categorised as <6, 6–9, or >9 hours. Restless sleep and sleep quality were each single questions, with ‘average’ restlessness and ‘average’ sleep quality as the reference group.

A one-stage approach to meta-analysis was used, so that the data from the participating eligible studies (Table 1) were included in a single model. Logistic regression models were used for the binary outcome. A fixed study effect and study site effect were included in the model specification as strata. Univariable analysis was performed to evaluate the association between the measures of SDB and maternal sleep patterns and the odds of late stillbirth. A multivariable model was developed incorporating prespecified covariates [38] available in all the studies (Appendix 1 in the S1 Protocol) and measures of SDB and maternal sleep patterns that were significant in univariable analysis (Table 1). Some covariates (habitual snoring, the BQ, sleep quality, restless sleep, daytime naps, daytime sleepiness using the ESS, and getting up to use the toilet) were not available in all participating studies (S1 Fig).

Table 1. Study level characteristics and measured sleep-related factors in participating studies.

Study level characteristics	The Auckland Stillbirth Study	Sydney Stillbirth Study	New Zealand Multicentre Stillbirth Study	Midlands and North of England Stillbirth Study	Study of Trends and Associated Risks for Stillbirth Study
Study level characteristics	Stacey et al (2011)⁶	Gordon et al (2015)⁹	McCowan et al (2017)⁴	Heazell et al (2017)⁸	O’Brien et al (2018)⁷
Location	Auckland, New Zealand	Sydney, Australia	New Zealand	United Kingdom	International
Years of recruitment	July 2006 to June 2009	January 2006 to December 2011	February 2012 to December 2015	April 2014 to March 2016	September 2012 to August 2014
Study design	Prospective population-based case-control	Prospective population-based case-control	Prospective population-based case-control	Prospective population-based case-control	Nested case-control with uncontrolled cohort
Population	Non-anomalous singleton pregnancy, ≥28 weeks’ gestation, from three health regions in Auckland, New Zealand	Non-anomalous singleton pregnancy, ≥32 weeks’ gestation, from nine tertiary maternity facilities in metropolitan Sydney, Australia	Non-anomolous singleton pregnancy, ≥28 weeks’ gestation, from seven health regions throughout New Zealand	Non-anomalous singleton pregnancy, ≥28 weeks’ gestation, from 41 maternity facilities in the United Kingdom	Singleton pregnancy, ≥28 weeks’ gestation, fluent in English, from 16 high, middle, and low income countries
Stated main outcome measure	Maternal snoring, daytime sleepiness, and sleep position at the time of going to sleep and on waking (left side, right side, back, and other)	Risk factors for late-pregnancy stillbirth with a particular focus on those risks that are potentially modifiable	The adjusted odds of late stillbirth associated with self-reported going-to-sleep position, on the last night	Maternal sleep practices pregnancy	To investigate, in an international cohort, whether maternal sleep practices are related to late stillbirth
Measured sleep-related factors	Sleep position (going-to-sleep, waking)	Sleep position	Sleep position (going-to-sleep, waking)	Sleep position (going-to-sleep, waking)	Sleep position (going-to-sleep, waking)
	Snoring presence		Snoring presence	Snoring presence	Snoring presence
	Sleep duration	Snoring presence	Sleep duration	Sleep duration	Sleep duration
	Sleep quality	Sleep duration	Sleep quality	Sleep quality	Sleep quality
	Sleep restlessness	Sleep quality	Sleep restlessness	Sleep restlessness	Sleep restlessness
	Getting up to toilet	Sleep restlessness	Getting up to toilet	Getting up to toilet	Getting up to toilet
	Daytime naps	Getting up to toilet	Daytime naps	Daytime naps	Daytime naps
	Epworth Sleepiness Scale	Daytime naps	Epworth Sleepiness Scale	Epworth Sleepiness Scale	Epworth Sleepiness Scale
	Sleep apnoea	Epworth Sleepiness Scale	Berlin Questionnaire	Berlin Questionnaire	Berlin Questionnaire
	Night waking	Berlin Questionnaire	Night waking	-	Night waking
	-	-	Restless legs	Restless legs	Restless legs
	-	-	Sleep latency	Sleep latency	Sleep latency
	-	-	Position changes	Position changes	Position changes
	-	-	Insomnia	Insomnia	Insomnia
	-	-	Bed size and side	Bed size and side	Bed size and side
	-	-	Pillow(s) placement	Pillow(s) placement	Pillow(s) placement
	-	-	Sleep partners	Sleep partners	Sleep partners
	-	-	Sleep advice	Sleep advice	-
	-	-	-	Sleep medication	Sleep medication
	-	-	Sleep chronotype	-	-
Time frames of measured sleep factors	Pre-pregnancy	Pre-pregnancy	-	Pre-pregnancy	Pre-pregnancy
	During pregnancy	During pregnancy	During pregnancy	During pregnancy	During pregnancy
	Last month	Last month	-	Last 4 weeks	Last 4 weeks
	-	Last two weeks	Last week	-	-
	-	-	-	Last week	Last week
	Last night	-	Last night	Last night	Last night
Data collection	Interview and clinical records	Interview and clinical records	Interview and clinical records	Interview and clinical records	Online survey

Open in a new tab

The interaction between supine going-to-sleep position and common measures of SDB (habitual snoring and the BQ) and sleep duration were assessed in bi-variable regression models. Significant interactions were then added to the multivariable model as described above. Estimates of the risk of late stillbirth were reported as odds ratio (OR) with 95% confidence intervals (95% CI). For missing data in each individual study, imputation was not undertaken. Statistical analyses were performed using SAS, version 9.4 (SAS Institute Inc., Cary NC USA).

Each individual study obtained ethical approval [26, 27, 30–32]. Approval for the IPD meta-analysis was obtained from the New Zealand Health and Disability Ethics Committee (NTX/06/05/054/AM06).

Results

Participants comprised 851 late stillbirth cases and 2257 controls with ongoing pregnancies from five eligible case-control studies (Fig 1): the Auckland Stillbirth Study [26], the New Zealand Multicentre Stillbirth Study [31], the Sydney Stillbirth Study [27], the UK Midlands and North of England Stillbirth Study [30], and the International Study of Trends and Associated Risks for Stillbirth Study [32], comprising women of many ethnicities [24].

Differences in maternal and pregnancy characteristics, infant size, and going-to-sleep position between cases and controls have been previously reported (S1 Table) [24]. ‘Any’ snoring (cases n = 473, 56.0%; controls, n = 1182, 54.1%), sleep quality (fairly bad to very bad, cases n = 248, 33.5%; controls, n = 703, 35.3%), daytime sleepiness (positive ESS score ≥10, cases n = 128, 17.5%; controls n = 312, 15.8%), and frequency of getting up to use the toilet (≥1 per night, cases n = 667, 90.0%; controls, n = 1820, 91.5%) last month were not associated with late stillbirth in the univariable analysis.

Long sleep duration >9 hours last month (cases n = 78, 10.5%; controls, n = 129, 6.5%) was independently associated with late stillbirth compared to sleep duration of 6 to 9 hours (adjusted odds ratio [aOR] 1.82, 95% CI 1.14–2.90) (Table 2). Reporting a daily daytime nap last month (cases n = 139, 23.7%; controls, n = 216, 12.8%) compared to never reporting a daytime nap was associated with an increase in the odds of late stillbirth (aOR 1.52, 95% CI 1.02–2.28). In addition, a positive BQ (cases n = 176, 30.0%; controls, n = 370, 21.8%) was associated with late stillbirth (aOR 1.44, 95% CI 1.02–2.04), however, when BMI >30 was removed from the BQ score, a positive BQ showed no significant association with stillbirth (aOR 0.81, 95% CI 0.54–1.21). Restless sleep greater than average last month (cases n = 225, 38.3%; controls, n = 761, 45.2%) was associated with a reduction in the odds of late stillbirth (aOR 0.62, 95% CI 0.44–0.88).

Table 2. Subjective indicators of sleep-disordered breathing and maternal sleep patterns in participating case-control studies and pooled IPD meta-analysis.

	TASS Stacey et al (2011) [26]		SSS Gordon et al (2015) [27]		MCSS McCowan et al (2017)[31]		MiNESS Heazell et al (2017) [30]		STARS O’Brien et al (2018) [32]		Collaborative Individual Participant Data of Going-to-sleep and Stillbirth (CRIBSS) analysis
Characteristic	Case	Control	Case	Control	Case	Control	Case	Control	Case	Control	Case	Control	Univariable odds ratio (95% CI)	Adjusted odds ratio (95% CI)
Total participants	155 (33.8)	304 (66.2)	103 (34.9)	192 (65.1)	163 (22.5)	560 (77.5)	288 (28.2)	733 (71.8)	142 (23.3)	468 (76.7)	851 (27.4)	2257 (72.6)
Going-to-sleep position (last two weeks)
Non-supine	104 (87.4)	242 (94.5)	84 (89.4)	183 (97.9)	139 (88.0)	539 (96.4)	254 (93.0)	698 (96.7)	124 (96.9)	355 (97.0)	705 (91.3)	2017 (96.5)	1	1
Supine	15 (12.6)	14 (4.5)	10 (10.6)	4 (2.1)	19 (12.0)	20 (3.6)	19 (7.0)	24 (3.3)	4 (3.1)	11 (3.0)	67 (8.7)	73 (3.5)	2.85 (2.01–4.05)	3.06 (1.77–5.28)
Snoring ‘any’ (during pregnancy)
No	86 (55.5)	175 (57.6)	49 (47.6)	93 (48.4)	59 (36.2)	255 (45.5)	118 (41.0)	300 (41.2)	59 (43.7)	179 (44.8)	371 (44.0)	1002 (45.9)	1	-
Yes	69 (44.5)	129 (42.4)	54 (52.4)	99 (51.6)	104 (63.8)	305 (54.5)	170 (59.0)	428 (58.8)	76 (56.3)	221 (55.2)	473 (56.0)	1182 (54.1)	1.11 (0.95–1.31)	-
Habitual snoring ≥ 3 nights/week (last month)
No	-	-	-	-	129 (79.1)	494 (88.2)	192 (74.7)	544 (81.1)	95 (76.6)	286 (76.5)	416 (76.5)	1324 (82.5)	1	1
Yes	-	-	-	-	34 (20.9)	66 (11.8)	65 (25.3)	127 (18.9)	29 (23.4)	88 (23.5)	128 (23.5)	281 (17.5)	1.40 (1.10–1.78)	1.04 (0.74–1.47)
Berlin Questionnaire
Negative screen	-	-	-	-	106 (65.0)	463 (82.7)	195 (67.7)	534 (72.9)	110 (80.9)	331 (81.7)	411 (70.0)	1328 (78.2)	1	1
Positive screen	-	-	-	-	57 (35.0)	97 (17.3)	93 (32.3)	199 (27.2)	26 (19.1)	74 (18.3)	176 (30.0)	370 (21.8)	1.52 (1.22–1.89)	1.44 (1.02–2.04)
Restless sleep (last month)
Less than average	-	-	-	-	73 (44.8)	276 (49.3)	109 (37.8)	214 (29.3)	47 (34.6)	95 (24.2)	229 (39.0)	585 (34.7)	1.00 (0.77–1.28)	1.08 (0.78–1.50)
Average	-	-	-	-	41 (25.1)	127 (22.7)	61 (21.2)	110 (15.0)	31 (22.8)	101 (25.7)	133 (22.7)	338 (20.1)	1	1
Greater than average	-	-	-	-	49 (30.1)	157 (28.0)	118 (41.0)	407 (55.7)	58 (42.6)	197 (54.1)	225 (38.3)	761 (45.2)	0.75 (0.59–0.97)	0.62 (0.44–0.88)
Sleep duration overnight (last month)
<6 hours	30 (19.4)	45 (14.8)	-	-	27 (16.5)	79 (14.1)	78 (27.1)	212 (29.1)	7 (5.1)	46 (11.4)	142 (19.1)	382 (19.1)	1.06 (0.85–1.33)	0.77 (0.55–1.07)
6–9 hours	104 (67.1)	233 (76.6)	-	-	123 (75.5)	452 (80.7)	179 (62.1)	477 (65.5)	116 (85.3)	321 (79.9)	522 (70.4)	1483 (74.4)	1	1
>9 hours	21 (13.5)	26 (8.6)	-	-	13 (8.0)	29 (5.2)	31 (10.8)	39 (5.4)	13 (9.6)	35 (8.7)	78 (10.5)	129 (6.5)	1.67 (1.23–2.26)	1.82 (1.14–2.90)
Daytime naps (last month)
Never	-	-	-	-	33 (26.4)	109 (28.0)	56 (44.8)	157 (40.4)	36 (28.8)	123 (31.6)	125 (21.3)	389 (23.1)	1	1
Occasionally	-	-	-	-	63 (32.1)	248 (36.1)	96 (49.0)	333 (48.4)	37 (18.9)	107 (15.6)	196 (33.4)	688 (40.8)	0.90 (0.69–1.17)	0.92 (0.66–1.30)
Often	-	-	-	-	28 (22.1)	133 (33.8)	66 (52.0)	149 (37.8)	33 (26.0)	112 (28.4)	127 (21.6)	394 (23.4)	1.03 (0.77–1.38)	0.91 (0.62–1.33)
Everyday	-	-	-	-	39 (28.1)	70 (32.4)	70 (50.4)	93 (43.1)	30 (21.6)	53 (24.5)	139 (23.7)	216 (12.8)	2.06 (1.52–2.78)	1.52 (1.02–2.28)
Daytime sleepiness screen (Epworth Sleepiness Scale) (last month)
Negative <10	136 (87.7)	270 (88.8)	-	-	129 (79.0)	479 (85.5)	244 (85.3)	612 (84.0)	96 (74.4)	302 (79.0)	604 (82.5)	1660 (84.2)	1	-
Positive ≥10–15	16 (10.3)	29 (9.5)	-	-	25 (15.4)	68 (12.2)	33 (11.5)	93 (12.7)	24 (18.6)	61 (16.0)	98 (13.4)	251 (12.7)	1.09 (0.84–1.41)	-
Positive >15	3 (1.9)	5 (1.6)			9 (5.6)	13 (2.3)	9 (3.2)	24 (3.3)	9 (7.0)	19 (5.0)	30 (4.1)	61 (3.1)	1.41 (0.89–2.23)	-
Sleep quality (last month)
Very good	20 (12.9)	32 (10.5)	-	-	25 (15.3)	92 (16.4)	33 (11.5)	49 (6.7)	9 (6.7)	18 (4.5)	87 (11.7)	191 (9.6)	1.26 (0.94–1.67)	-
Good to average	79 (51.0)	170 (55.9)	-	-	98 (60.1)	362 (64.6)	146 (50.7)	377 (51.5)	83 (61.5)	190 (47.9)	406 (54.8)	1099 (55.1)	1	-
Fairly bad	42 (27.1)	79 (26.0)	-	-	27 (16.6)	80 (14.3)	82 (28.5)	220 (30.1)	33 (24.4)	159 (40.1)	184 (24.8)	538 (27.0)	0.93 (0.75–1.14)	-
Very bad	14 (9.0)	23 (7.6)	-	-	13 (8.0)	26 (4.7)	27 (9.4)	86 (11.8)	10 (7.4)	30 (7.6)	64 (8.7)	165 (8.3)	1.03 (0.75–1.42)	-
Frequency of getting up to use the toilet overnight (last month)
<1	19 (12.3)	36 (11.8)	-	-	12 (3.4)	39 (7.0)	38 (13.2)	78 (10.6)	5 (3.7)	16 (4.1)	74 (10.0)	169 (8.5)	1.07 (0.80–1.45)	-
≥1	136 (87.7)	268 (88.2)	-	-	151 (92.6)	521 (93.0)	250 (86.8)	655 (89.4)	130 (96.3)	376 (95.9)	667 (90.0)	1820 (91.5)	1	-

Open in a new tab

Data are number (percentage) or median (IQR). TASS = The Auckland Stillbirth Study. SSS = Sydney Stillbirth Study. MCSS = New Zealand Multicentre Stillbirth Study. MiNESS = Midlands and North of England Stillbirth Study. STARS = Study of Trends and Associated Risks for Stillbirth Study. Participants with missing data were excluded from the multivariable models. No imputation for missing data. Multivariable models are adjusted for matching terms (gestation at interview or survey in controls, and diagnosis of stillbirth for cases), study and site, age, BMI, ethnicity, parity, education, marital status, pre-existing hypertension or diabetes, smoking, drug use, baby birthweight centile, fetal movement, supine going-to-sleep position, habitual snoring, the Berlin Questionnaire, restless sleep, sleep duration, and daytime naps.

Women who had a stillbirth, 689 cases from four participating studies [27, 30–32], were asked what time of day they thought their baby had died: 34.8% (n = 240, or 52.3% of 459 cases who could recall a time of day) reported that they thought their baby had died overnight, 19.4% (n = 134) reported afternoon-evening, 11.8% (n = 81) morning, 0.6% (n = 4) during a daytime nap, and 33.4% (n = 230) were unsure (Fig 2).

Interactions were assessed between supine going-to-sleep position and habitual snoring, a positive BQ including BMI, sleep duration >9 hours, and restless sleep greater than average last month (Table 3). Interactions for a positive BQ (p = 0.56), sleep duration >9 hours (p = 0.99), and restless sleep greater than average (p = 0.98) were not statistically significant. There was a significant interaction between habitual snoring and supine going-to-sleep position (multivariable interaction p value = 0.001). The combined effect of supine going-to-sleep position and habitual snoring resulted in a reduced odds of late stillbirth in the multivariable model than would be expected. (Table 3).

Table 3. Analysis for interaction between supine going-to-sleep position, and habitual snoring, the Berlin Questionnaire, sleep duration >9 hours and restless sleep greater than average.

	Sleep factor	Supine position	n	%	Univariable odds ratio (95% CI)	Univariable interaction p value	Multivariable odds ratio (95% CI)	Multivariable interaction p value
Habitual snoring	Yes	Yes	17	0.8	1.44 (0.50–4.18)	0.04	1.03 (0.29–3.64)	0.001
	Yes	No	382	18.4	1.49 (1.16–1.92)		1.17 (0.82–1.66)
	No	Yes	75	3.6	3.37 (2.08–5.45)		3.75 (2.02–6.95)
	No	No	1606	77.2	1		1
Positive Berlin Questionnaire	Yes	Yes	22	1.0	3.44 (1.45–8.12)	0.56	-	-
	Yes	No	510	23.1	1.56 (1.24–1.95)		-
	No	Yes	75	3.4	2.96 (1.83–4.80)		-
	No	No	1599	72.5	1		-
Sleep duration >9hrs	Yes	Yes	12	0.5	4.10 (1.28–13.13)	0.99	-	-
	Yes	No	178	6.9	1.55 (1.11–2.15)		-
	No	Yes	114	4.4	2.63 (1.78–3.88)		-
	No	No	2271	88.2	1		-
Restless sleep greater than average	Yes	Yes	34	1.5	1.19 (0.56–2.54)	0.10	-	-
	Yes	No	916	41.7	3.45 (2.05–5.80)		-
	No	Yes	63	2.9	0.75 (0.61–0.93)		-
	No	No	1186	53.9	1		-

Open in a new tab

Participants with missing data were excluded from the analysis. No imputation for missing data.

Discussion

Main findings

Our study has demonstrated that a positive BQ, long sleep duration >9 hours, and a daily daytime nap in the last month, were each associated with increased odds of late stillbirth. In contrast, restless sleep greater than average in the last month was protective for late stillbirth. The associations between these aspects of maternal sleep and late stillbirth were adjusted for prespecified covariates [38] available in all the studies (S 1), and measures of SDB and maternal sleep patterns significant in univariable analysis (Table 1).

The ~50% prevalence of ‘any’ snoring and habitual snoring ≥3 nights per week between 17–24% was within the range reported in the pregnancy literature [4, 43–46]. ‘Any’ snoring, habitual snoring, sleep quality, and daytime sleepiness using the ESS, was not associated with late stillbirth (Table 2). This is consistent with previous studies: snoring [26, 27, 33], sleep quality [33], and daytime sleepiness [47].

A positive BQ was independently associated with late stillbirth (Table 2), although this association was no longer significant when BMI >30 was excluded from the BQ (Model 2). This aligns with the suggestion [48, 49] that the BQ used in pregnant women is a proxy for BMI during late pregnancy, due to BMI being a component of the BQ. Indeed, the BQ performs poorly as a screening tool for objective SDB measures during pregnancy, with a 2018 meta-analysis [47] of six studies (n = 604 participants) reporting poor to fair BQ performance during pregnancy with an overall probability of OSA occurrence of 38% if a pregnant woman has a positive BQ. This range may be due to the BQ including risk factors that do not apply to pregnant women (male gender, age >50 years) and because weight gain is relevant for all pregnancies. Furthermore, symptoms of SDB progress with gestation, and there are differing opinions about the optimal timing of the BQ during pregnancy [47].

Long sleep duration >9 hours was also associated with late stillbirth (Table 2), and this association has previously been reported in two case-control studies [26, 32]. While the reason is uncertain, it is plausible that prolonged periods of aortocaval compression [36, 37] during maternal sleep may be a factor. It is also possible that an unmeasured confounder associated with long third trimester sleep (e.g. working night shifts or no paid employment) [50] may lengthen the duration of maternal sleep over the last month and contribute to stillbirth. The definition of long duration in the individual case-control studies is also inconsistent, ranging from >8 hours [26] to >9 hours [32]. This range may be due to lack of consensus about what is considered normal sleep duration in healthy pregnancy [51], although self-reported time to sleep in the third trimester is similar to objectively measured sleep duration [51] and maternal estimates of sleep duration increases in accuracy with increasing duration of sleep [52]. There was no association between short sleep duration during last month and late stillbirth, despite an independent association with short sleep on the night before stillbirth in three case-control studies [26, 30, 31]. This discrepancy may be due to a potentially fatal fetal event (e.g. pre-labour contractions for an acutely compromised fetus) that may shorten sleep on the night before stillbirth [53].

Daily daytime naps were also associated with a 1.5-fold increase in the odds of late stillbirth compared with no daytime naps (Table 2), and this finding is consistent with individual studies [26, 30, 31]. The physiology behind this is unknown and cannot be explained by overnight sleep duration or daytime sleepiness, as daily naps remained significant when we controlled for these factors. However, we speculate that daily naps in late pregnancy may increase the duration of maternal inactivity, potentially increasing the amount of time that the women spend in the supine position and therefore the duration of aortocaval compression, which when combined with the blood pressure dips that occur during third trimester sleep [54], may further compromise a vulnerable fetus [34].

Our finding of a 38% reduction in the odds of late stillbirth for women who reported restless sleep more than average during the last month is novel (Table 2). We speculate that this may be due to maternal body movement facilitating maternal-fetal blood flow, potentially abating adverse fetal effects of aortocaval compression [37, 55]. Furthermore, while maternal hypotension is known to have adverse fetal consequences, such as lower birth weight and stillbirth [56–59], increased third trimester arousals related to snoring [60] may assuage prolonged periods of relative hypotension, as deep sleep is commensurate with the lowest overnight blood pressure and arousal with increased blood pressure [61]. Our finding of a protective association between restless sleep more than average and late stillbirth aligns with an international case-control study [32] that reported non-restless sleep in the last month was associated with a 1.7-fold increase in odds of late stillbirth. Similarly, getting up to use the toilet on the night before stillbirth is associated with a 2-fold reduction in late stillbirth [26, 30, 31], suggesting that maternal body movement on the night before stillbirth may mitigate the effects of a hypoxic event on the fetus [62].

Certainly, pregnant women are susceptible to the development of sleep disturbances, commonly reduced quality and duration of sleep, night waking, daytime sleepiness, and snoring [45, 63]. Causes are most likely to be hormonal and physiological changes of pregnancy, including increased oxygen consumption and metabolic rate, lower overall oxygen reserve, nasopharyngeal oedema, vasomotor rhinitis, and weight gain, which contribute to narrowing of upper airway, reduced functional residual capacity due to diaphragmatic pressure by the growing fetus, and increased arousals during sleep [60, 63]. These physiological changes are exacerbated as pregnancy progresses and when combined with obesity, advanced maternal age, and supine sleep position [64–66].

Conversely, late pregnancy may provide some protection from SDB, with increased respiratory drive [67], alteration in the cyclical sleep pattern with decreased rapid eye movement (REM) sleep [60, 63, 68], and preference for a lateral sleep position [26, 30, 45, 69]. These may be factors contributing to our finding of a significant interaction between habitual snoring during the last month and supine going-to-sleep position, with a lower odds of late stillbirth than expected in women who reported both during the last month. While this may be a chance finding due to low prevalence, with 17 (12 controls and 5 cases) of 92 women reporting habitual snoring and a supine going-to-sleep position, this could also be explained by the women being woken by a sleep companion or experiencing a self-arousal due to snoring, and moving from the supine to a lateral position, which is known to reduce third trimester snoring in obese women [23] and late stillbirth risk [24].

Strengths and limitations

A limitation of the IPD meta-analysis is that not all participating studies had data for all sleep measures. Minor differences in the design of the individual studies also limited the inclusion of some covariates. Our search had no language restriction and an eligible study from India was identified, however, there was no response from authors or journal editors to repeated invitations to participate. No other eligible randomised trials, prospective cohort studies or studies from low-income countries were identified, thus participating studies were all case-control studies from high-income countries. A limitation of case-control studies include the retrospective data collection which is subject to potential recall bias, although as the relationship between late stillbirth and maternal sleep is not universally well known by pregnant women, systematic bias is unlikely. The longer length of time before interview for cases may have influenced their recall compared to controls, however, case recall is unlikely to be biased towards an association with SDB, with self-reports from a single night of sleep having similar bias and calibration as ‘usual’ sleep [70]. Use of self-reported symptoms of SDB, rather than objective measures using polysomnography may also be considered a limitation. However, self-report of snoring is strongly and reliably associated with the severity of OSA obtained from polysomnography in non-pregnant [71] and pregnant women [46], therefore self-report is useful for large scale studies where routine access to polysomnography in late pregnancy is costly and impractical.

Conclusion

This IPD meta-analysis adds to the evidence on maternal sleep and late stillbirth, using the best available data on the association of SDB and maternal sleep patterns with the risk of late stillbirth. These findings demonstrate that self-reported maternal snoring, a positive BQ screen excluding BMI, daytime sleepiness, sleep quality, and getting up to use the toilet, are not independently associated with late stillbirth last month. Long sleep duration >9 hours and daily daytime naps are independent risk factors, while sleep more restless than average may reduce the odds of late stillbirth. There is an urgent need to better understand factors associated with long sleep duration and daily daytime naps before recommendations can be made to pregnant women. Meanwhile, pregnant women may be reassured that the commonly reported increased restlessness of sleep during late pregnancy may be physiological and is associated with a reduced risk of late stillbirth.

Supporting information

S1 Fig. Chart of available data from contributing studies.

(DOCX)

Click here for additional data file.^{(93.5KB, docx)}

S1 Table. Participant level characteristics and non-sleep late stillbirth risk factors in participating case-control studies and pooled IPD meta-analysis.

(DOCX)

Click here for additional data file.^{(32.5KB, docx)}

S1 Checklist. PRISMA-P (Preferred reporting items for systematic review and meta-analysis protocols) 2015 checklist: Recommended items to address in a systematic review protocol*.

(DOC)

Click here for additional data file.^{(82KB, doc)}

S1 Protocol

(PDF)

Click here for additional data file.^{(355.6KB, pdf)}

Acknowledgments

We would like to thank the women who participated in the individual studies and the research midwives who conducted the interviews.

Data Availability

Data cannot be shared publicly beyond the Collaborative Individual Participant Data Meta-analysis of Sleep and Stillbirth (CRIBSS) group as no individual participating study obtained consent from participants to make the data publically available. Furthermore, because stillbirth is uncommon there is potential for participants to be identifiable. Contact information for the CRIBSS Data Access Committee is The CRIBSS Data Centre, Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142.

Funding Statement

Mrs Cronin reports grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), grants from Sir John Logan Campbell Medical Trust, during the conduct of the study; Ms. Wilson reports grants from 2016 TransTasman Red Nose/Curekids (6601); Dr. Gordon reports grants from Stillbirth Foundation Australia, during the conduct of the study; other from NHMRC Early Career Fellowship #1089898, outside the submitted work; Dr. Li reports grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), during the conduct of the study; Dr. Culling has nothing to disclose; Associate Professor Raynes-Greenow reports grants from Stillbirth Foundation Australia, during the conduct of the study; other from NHMRC Career Development Fellowship #1087062, outside the submitted work; Professor Heazell reports grants from Action Medical Research, during the conduct of the study; grants from Tommy’s, grants from NIHR, outside the submitted work; Dr. Stacey reports grants from Cure Kids (3537), Nurture Foundation, Auckland District Health Board Charitable Trust., grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., during the conduct of the study; Professor Askie has nothing to disclose; Professor Mitchell reports grants from Cure Kids (Grant 3537), Nurture Foundation, Auckland District Health Board Trust., grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), during the conduct of the study; other from Cure Kids, outside the submitted work; Associate Professor Thompson reports grants from Cure Kids (3537), Nurture Foundation, Auckland District Health Board Charitable Trust., grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), during the conduct of the study; Professor McCowan reports grants from Cure Kids (537), Nurture Foundation, Auckland District Health Board Trust., grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), during the conduct of the study. Associate Professor O’Brien reports grants from American Sleep Medicine Foundation, grants from ResMed, outside the submitted work.

References

1.Heazell A, Siassakos D, Blencowe H, Burden C, Bhutta Z, Cacciatore J, et al. Stillbirths: economic and psychosocial consequences. Lancet. 2016;387(10018):604–16. 10.1016/S0140-6736(15)00836-3 [DOI] [PubMed] [Google Scholar]
2.Reinebrant HE, Leisher SH, Coory M, Henry S, Wojcieszek AM, Gardener G, et al. Making stillbirths visible: a systematic review of globally reported causes of stillbirth. BJOG: An International Journal of Obstetrics & Gynaecology. 2017. [DOI] [PubMed] [Google Scholar]
3.Flenady V, Wojcieszek A, Middleton P, Ellwood D, Erwich J, Coory M, et al. Stillbirths: Recall to action in high-income countries. Lancet. 2016;387:691–702. 10.1016/S0140-6736(15)01020-X [DOI] [PubMed] [Google Scholar]
4.O’Brien LM, Bullough AS, Owusu JT, Tremblay KA, Brincat CA, Chames MC, et al. Pregnancy-onset habitual snoring, gestational hypertension, and preeclampsia: prospective cohort study. Am J Obstet Gynecol. 2012;207(6):487.e1–.e9. [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Bourjeily G, Raker C, Chalhoub M, Miller M. Pregnancy and fetal outcomes of symptoms of sleep-disordered breathing. Eur Respir J. 2010;36(4):849–55. 10.1183/09031936.00021810 [DOI] [PubMed] [Google Scholar]
6.Izci B, Martin SE, Dundas KC, Liston WA, Calder AA, Douglas NJ. Sleep complaints: snoring and daytime sleepiness in pregnant and pre-eclamptic women. Sleep Med. 2005;6(2):163–9. 10.1016/j.sleep.2004.12.007 [DOI] [PubMed] [Google Scholar]
7.Facco FL, Parker CB, Reddy UM, Silver RM, Koch MA, Louis JM, et al. Association between sleep-disordered breathing and hypertensive disorders of pregnancy and gestational diabetes mellitus. Obstet Gynecol. 2017;129(1):31 10.1097/AOG.0000000000001805 [DOI] [PMC free article] [PubMed] [Google Scholar]
8.Pien GW, Pack AI, Jackson N, Maislin G, Macones GA, Schwab RJ. Risk factors for sleep-disordered breathing in pregnancy. Thorax. 2013:thoraxjnl-2012-202718. [DOI] [PMC free article] [PubMed]
9.Bin YS, Cistulli PA, Ford JB. Population-based study of sleep apnea in pregnancy and maternal and infant outcomes. J Clin Sleep Med. 2016;12(06):871–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
10.Williams MA, Miller RS, Qiu C, Cripe SM, Gelaye B, Enquobahrie D. Associations of early pregnancy sleep duration with trimester-specific blood pressures and hypertensive disorders in pregnancy. Sleep. 2010;33(10):1363–71. 10.1093/sleep/33.10.1363 [DOI] [PMC free article] [PubMed] [Google Scholar]
11.Facco FL, Grobman WA, Kramer J, Ho KH, Zee PC. Self-reported short sleep duration and frequent snoring in pregnancy: impact on glucose metabolism. Am J Obstet Gynecol. 2010;203(2):142.e1–.e5. [DOI] [PMC free article] [PubMed] [Google Scholar]
12.Qiu C, Enquobahrie D, Frederick IO, Abetew D, Williams MA. Glucose intolerance and gestational diabetes risk in relation to sleep duration and snoring during pregnancy: a pilot study. BMC Womens Health. 2010;10(1):17. [DOI] [PMC free article] [PubMed] [Google Scholar]
13.Reutrakul S, Zaidi N, Wroblewski K, Kay HH, Ismail M, Ehrmann DA, et al. Sleep disturbances and their relationship to glucose tolerance in pregnancy. Diabetes Care. 2011;34(11):2454–7. 10.2337/dc11-0780 [DOI] [PMC free article] [PubMed] [Google Scholar]
14.Micheli K, Komninos I, Bagkeris E, Roumeliotaki T, Koutis A, Kogevinas M, et al. Sleep patterns in late pregnancy and risk of preterm birth and fetal growth restriction. Epidemiology. 2011:738–44. 10.1097/EDE.0b013e31822546fd [DOI] [PubMed] [Google Scholar]
15.Abeysena C, Jayawardana P, Seneviratne RDA. Maternal sleep deprivation is a risk factor for small for gestational age: a cohort study. Aust N Z J Obstet Gynaecol. 2009;49(4):382–7. 10.1111/j.1479-828X.2009.01010.x [DOI] [PubMed] [Google Scholar]
16.Fung AM, Wilson DL, Lappas M, Howard M, Barnes M, O’Donoghue F, et al. Effects of maternal obstructive sleep apnoea on fetal growth: a prospective cohort study. PLoS One. 2013;8(7):e68057 10.1371/journal.pone.0068057 [DOI] [PMC free article] [PubMed] [Google Scholar]
17.Pamidi S, Marc I, Simoneau G, Lavigne L, Olha A, Benedetti A, et al. Maternal sleep-disordered breathing and the risk of delivering small for gestational age infants: a prospective cohort study. Thorax. 2016;71(8):719–25. 10.1136/thoraxjnl-2015-208038 [DOI] [PubMed] [Google Scholar]
18.O’Brien LM, Bullough AS, Owusu JT, Tremblay KA, Brincat CA, Chames MC, et al. Snoring during pregnancy and delivery outcomes: a cohort study. Sleep. 2013;36(11):1625–32. 10.5665/sleep.3112 [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Kneitel AW, Treadwell MC, O’Brien LM. Effects of maternal obstructive sleep apnea on fetal growth: a case-control study. J Perinatol. 2018;38(8):982 10.1038/s41372-018-0127-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
20.Li R, Zhang J, Zhou R, Liu J, Dai Z, Liu D, et al. Sleep disturbances during pregnancy are associated with cesarean delivery and preterm birth. J Matern-Fetal Neonatal Med. 2017;30(6):733–8. 10.1080/14767058.2016.1183637 [DOI] [PubMed] [Google Scholar]
21.Kajeepeta S, Sanchez SE, Gelaye B, Qiu C, Barrios YV, Enquobahrie DA, et al. Sleep duration, vital exhaustion, and odds of spontaneous preterm birth: a case-control study. BMC Pregnancy Childbirth. 2014;14:337 10.1186/1471-2393-14-337 [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Dunietz GL, Shedden K, Schisterman EF, Lisabeth LD, Treadwell MC, O’Brien LM. Associations of snoring frequency and intensity in pregnancy with time-to-delivery. Paediatr Perinat Epidemiol. 2018;32(6):504–11. 10.1111/ppe.12511 [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Ura M, Fujimoto K. Relationship between sleep-disordered breathing and sleeping position at the 37th week of pregnancy: an observational cross-sectional study. Sleep Biol Rhythms. 2018;16(4):441–7. [Google Scholar]
24.Cronin RS, Li M, Thompson JMD, Gordon A, Raynes-Greenow CH, Heazell AEP, et al. An Individual Participant Data Meta-analysis of Maternal Going-to-Sleep Position, Interactions with Fetal Vulnerability, and the Risk of Late Stillbirth. EClinicalMedicine. 2019;10:49–57. 10.1016/j.eclinm.2019.03.014 [DOI] [PMC free article] [PubMed] [Google Scholar]
25.Warland J, Dorrian J, Morrison JL, O’Brien LM. Maternal sleep during pregnancy and poor fetal outcomes: A scoping review of the literature with meta-analysis. Sleep Med Rev. 2018;41:197–219. 10.1016/j.smrv.2018.03.004 [DOI] [PubMed] [Google Scholar]
26.Stacey T, Thompson J, Mitchell EA, Ekeroma AJ, Zuccollo JM, McCowan LM. Association between maternal sleep practices and risk of late stillbirth: a case-control study. BMJ. 2011;342:d3403 10.1136/bmj.d3403 [DOI] [PMC free article] [PubMed] [Google Scholar]
27.Gordon A, Raynes-Greenow C, Bond D, Morris J, Rawlinson W, Jeffery H. Sleep position, fetal growth restriction, and late-pregnancy stillbirth: the Sydney stillbirth study. Obstet Gynecol. 2015;125:347–55. 10.1097/AOG.0000000000000627 [DOI] [PubMed] [Google Scholar]
28.Louis J, Auckley D, Miladinovic B, Shepherd A, Mencin P, Kumar D, et al. Perinatal outcomes associated with obstructive sleep apnea in obese pregnant women. Obstet Gynecol. 2012;120(5). [DOI] [PMC free article] [PubMed] [Google Scholar]
29.Louis JM, Mogos MF, Salemi JL, Redline S, Salihu HM. Obstructive sleep apnea and severe maternal-infant morbidity/mortality in the United States, 1998–2009. Sleep. 2014;37(5):843–9. 10.5665/sleep.3644 [DOI] [PMC free article] [PubMed] [Google Scholar]
30.Heazell A, Li M, Budd J, Thompson J, Stacey T, Cronin R, et al. Association between maternal sleep practices and late stillbirth–findings from a stillbirth case-control study. BJOG. 2017;125:254–62. 10.1111/1471-0528.14967 [DOI] [PMC free article] [PubMed] [Google Scholar]
31.McCowan L, Thompson J, Cronin R, Li M, Stacey T, Stone P, et al. Going to sleep in the supine position is a modifiable risk factor for late pregnancy stillbirth; Findings from the New Zealand multicentre stillbirth case-control study. PLoS One. 2017;12:e0179396 10.1371/journal.pone.0179396 [DOI] [PMC free article] [PubMed] [Google Scholar]
32.O’Brien LM, Warland J, Stacey T, Heazell AE, Mitchell EA, on behalf of the STARS Consortium. Maternal sleep practices and stillbirth: Findings from an international case-control study. Birth. 2019:1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
33.Owusu JT, Anderson FJ, Coleman J, Oppong S, Seffah JD, Aikins A, et al. Association of maternal sleep practices with pre-eclampsia, low birth weight, and stillbirth among Ghanaian women. Int J Gynaecol Obstet. 2013;121:261–5. 10.1016/j.ijgo.2013.01.013 [DOI] [PMC free article] [PubMed] [Google Scholar]
34.Warland J, Mitchell EA. A triple risk model for unexplained late stillbirth. BMC Pregnancy Childbirth. 2014;14:142 10.1186/1471-2393-14-142 [DOI] [PMC free article] [PubMed] [Google Scholar]
35.Izci-Balserak B, Pien GW. Sleep-disordered breathing and pregnancy: potential mechanisms and evidence for maternal and fetal morbidity. Curr Opin Pulm Med. 2010;16(6):574 10.1097/MCP.0b013e32833f0d55 [DOI] [PMC free article] [PubMed] [Google Scholar]
36.Kerr M, Scott D, Samuel E. Studies of the inferior vena cava in late pregnancy. BMJ. 1964;1:522–4. [PMC free article] [PubMed] [Google Scholar]
37.Humphries A, Ali Mirjalili S, Tarr GP, Thompson JM, Stone P. The effect of supine positioning on maternal hemodynamics during late pregnancy. The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2018:1–8. [DOI] [PubMed] [Google Scholar]
38.Li M, Thompson JM, Cronin RS, Gordon A, Raynes-Greenow C, Heazell AE, et al. The Collaborative IPD of Sleep and Stillbirth (Cribss): is maternal going-to-sleep position a risk factor for late stillbirth and does maternal sleep position interact with fetal vulnerability? An individual participant data meta-analysis study protocol. BMJ Open. 2018;8:e020323 10.1136/bmjopen-2017-020323 [DOI] [PMC free article] [PubMed] [Google Scholar]
39.Morgan R. The ROBINS-E tool (Risk Of Bias In Non-randomized Studies—of Exposures) [Internet]: University of Bristol; 2017. [https://www.bristol.ac.uk/population-health-sciences/centres/cresyda/barr/riskofbias/robins-e/ [Google Scholar]
40.World Health Organization. Neonatal and perinatal mortality for the year 2000: country, regional and global estimates [Internet] Geneva: World Health Organization; 2006. [http://whqlibdoc.who.int/publications/2006/9241563206_eng.pdf [Google Scholar]
41.Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the berlin questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med. 1999;131(7):485–91. 10.7326/0003-4819-131-7-199910050-00002 [DOI] [PubMed] [Google Scholar]
42.Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14. [DOI] [PubMed] [Google Scholar]
43.Franklin KA, Holmgren PA, Jonsson F, Poromaa N, Stenlund H, Svanborg E. Snoring, pregnancy-induced hypertension, and growth retardation of the fetus. Chest. 2000;117(1):137–41. 10.1378/chest.117.1.137 [DOI] [PubMed] [Google Scholar]
44.Ursavas A, Karadag M, Nalcı N, Ercan I, Gozu RO. Self-reported snoring, maternal obesity and neck circumference as risk factors for pregnancy-induced hypertension and preeclampsia. Respiration. 2007;76(1):33–9. 10.1159/000107735 [DOI] [PubMed] [Google Scholar]
45.Hutchison B, Stone P, McCowan L, Stewart A, Thompson J, Mitchell E. A postal survey of maternal sleep in late pregnancy. BMC Pregnancy Childbirth. 2012;12. [DOI] [PMC free article] [PubMed] [Google Scholar]
46.Louis JM, Koch MA, Reddy UM, Silver RM, Parker CB, Facco FL, et al. Predictors of sleep-disordered breathing in pregnancy. Am J Obstet Gynecol. 2018;218(5):521.e1–.e12. [DOI] [PMC free article] [PubMed] [Google Scholar]
47.Tantrakul V, Numthavaj P, Guilleminault C, McEvoy M, Panburana P, Khaing W, et al. Performance of screening questionnaires for obstructive sleep apnea during pregnancy: A systematic review and meta-analysis. Sleep Med Rev. 2016. [DOI] [PubMed] [Google Scholar]
48.Antony KM, Agrawal A, Arndt ME, Murphy AM, Alapat PM, Guntupalli KK, et al. Association of Adverse Perinatal Outcomes with Screening Measures of Obstructive Sleep Apnea. Am J Perinatol. 2011;28(8):651–8. [DOI] [PubMed] [Google Scholar]
49.O’Brien LM, Levine R, Dunietz GL, Bullough AS, Chames MC, MC T. Use of the Berlin Questionnaire in Pregnancy Primarily Identifies Obesity Not Sleep-Disordered Breathing. Under review. 2019.
50.Signal TL, Paine S-J, Sweeney B, Priston M, Muller D, Smith A, et al. Prevalence of abnormal sleep duration and excessive daytime sleepiness in pregnancy and the role of socio-demographic factors: comparing pregnant women with women in the general population. Sleep Med. 2014;15(12):1477–83. 10.1016/j.sleep.2014.07.007 [DOI] [PubMed] [Google Scholar]
51.Ladyman C, Signal TL. Sleep health in pregnancy: a scoping review. Sleep Med Clin. 2018;13(3):307–33. 10.1016/j.jsmc.2018.04.004 [DOI] [PubMed] [Google Scholar]
52.McIntyre J, Ingham C, Hutchinson B, Thompson J, McCowan L, Stone P, et al. A description of sleep behaviour in healthy late pregnancy, and the accuracy of self-reports. BMC Pregnancy Childbirth. 2016;16:1–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
53.Beebe KR, Lee KA. Sleep disturbance in late pregnancy and early labor. The Journal of perinatal & neonatal nursing. 2007;21(2):103–8. [DOI] [PubMed] [Google Scholar]
54.Taylor RS, Gamble G, McCowan L, North RA. Sleep effects on ambulatory blood pressure measurements in pregnant women. Am J Hypertens. 2001;14(1):38–43. 10.1016/s0895-7061(00)01226-7 [DOI] [PubMed] [Google Scholar]
55.Jeffreys R, Stepanchak W, Lopez B, Hardis J, Clapp J. Uterine blood flow during supine rest and exercise after 28 weeks of gestation. BJOG. 2006;113:1239–47. 10.1111/j.1471-0528.2006.01056.x [DOI] [PubMed] [Google Scholar]
56.Steer PJ, Little MP, Kold-Jensen T, Chapple J, Elliott P. Maternal blood pressure in pregnancy, birth weight, and perinatal mortality in first births: prospective study. BMJ. 2004;329(7478):1312 10.1136/bmj.38258.566262.7C [DOI] [PMC free article] [PubMed] [Google Scholar]
57.Ng PH, Walters WAW. The effects of chronic maternal hypotension during pregnancy. Aust N Z J Obstet Gynaecol. 1992;32(1):14–6. 10.1111/j.1479-828x.1992.tb01888.x [DOI] [PubMed] [Google Scholar]
58.Friedman EA, Neff RK. Hypertension-Hypotension in Pregnancy: Correlation With Fetal Outcome. JAMA. 1978;239(21):2249–51. [PubMed] [Google Scholar]
59.Warland J, McCutcheon H, Baghurst P. Maternal blood pressure in pregnancy and stillbirth: a case-control study of third-trimester stillbirth. Am J Perinatol. 2008;25(05):311–7. [DOI] [PubMed] [Google Scholar]
60.Wilson DL, Barnes M, Ellett L, Permezel M, Jackson M, Crowe SF. Decreased sleep efficiency, increased wake after sleep onset and increased cortical arousals in late pregnancy. Aust N Z J Obstet Gynaecol. 2011;51(1):38–46. 10.1111/j.1479-828X.2010.01252.x [DOI] [PubMed] [Google Scholar]
61.Javaheri S, Redline S. Sleep, slow-wave sleep, and blood pressure. Curr Hypertens Rep. 2012;14(5):442–8. 10.1007/s11906-012-0289-0 [DOI] [PubMed] [Google Scholar]
62.Thurlow J, Kinsella S. Intrauterine resuscitation: active management of fetal distress. Int J Obstet Anesth. 2002;11(2):105–16. 10.1054/ijoa.2001.0933 [DOI] [PubMed] [Google Scholar]
63.Pien GW, Schwab RJ. Sleep disorders during pregnancy. Sleep. 2004;27:1405–17. 10.1093/sleep/27.7.1405 [DOI] [PubMed] [Google Scholar]
64.Okun ML, Roberts JM, Marsland AL, Hall M. How disturbed sleep may be a risk factor for adverse pregnancy outcomes. Obstet Gynecol Surv. 2009;64(4):273–80. 10.1097/OGX.0b013e318195160e [DOI] [PMC free article] [PubMed] [Google Scholar]
65.Robertson N, Turner J, Kumar S. Pathophysiological changes associated with sleep disordered breathing and supine sleep position in pregnancy. Sleep Med Rev. 2019;46:1–8. 10.1016/j.smrv.2019.04.006 [DOI] [PubMed] [Google Scholar]
66.Hegewald MJ, Crapo RO. Respiratory physiology in pregnancy. Clin Chest Med. 2011;32(1):1–13. 10.1016/j.ccm.2010.11.001 [DOI] [PubMed] [Google Scholar]
67.Brownell L, West P, Kryger M. Breathing during Sleep in Normal Pregnant Women 1–3. Am Rev Respir Dis. 1986;133(1):38–41. 10.1164/arrd.1986.133.1.38 [DOI] [PubMed] [Google Scholar]
68.Driver HS, Shapiro CM. A Longitudinal Study of Sleep Stages in Young Women During Pregnancy and Postpartum. Sleep. 1992;15(5):449–53. 10.1093/sleep/15.5.449 [DOI] [PubMed] [Google Scholar]
69.Mills G, Chaffe A. Sleeping positions adopted by pregnant women of more than 30 weeks gestation. Anaesthesia. 1994;49(3):249–50. 10.1111/j.1365-2044.1994.tb03433.x [DOI] [PubMed] [Google Scholar]
70.Lauderdale DS, Knutson KL, Yan LL, Liu K, Rathouz PJ. Sleep duration: how well do self-reports reflect objective measures? The CARDIA Sleep Study. Epidemiology. 2008;19(6):838–45. [DOI] [PMC free article] [PubMed] [Google Scholar]
71.Bliwise DL, Nekich JC, Dement WC. Relative validity of self-reported snoring as a symptom of sleep apnea in a sleep clinic population. Chest. 1991;99(3):600–8. [DOI] [PubMed] [Google Scholar]

PLoS One. doi: 10.1371/journal.pone.0230861.r001

Decision Letter 0

Claudio Liguori

5 Jan 2020

PONE-D-19-22011

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

PLOS ONE

Dear Mrs Cronin,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

We would appreciate receiving your revised manuscript by Feb 19 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Claudio Liguori

Academic Editor

PLOS ONE

Journal Requirements:

1. When submitting your revision, we need you to address these additional requirements.

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

3. Thank you for stating the following in the Financial Disclosure section:

Ms. Wilson reports grants from 2016 TransTasman Red Nose/Curekids (6601);

Dr. Gordon reports grants from Stillbirth Foundation Australia, during the conduct of the study; other from NHMRC Early Career Fellowship #1089898, outside the submitted work;

Dr. Li reports grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), during the conduct of the study;

Dr. Culling has nothing to disclose;

Associate Professor Raynes-Greenow reports grants from Stillbirth Foundation Australia, during the conduct of the study; other from NHMRC Career Development Fellowship #1087062, outside the submitted work;

Professor Heazell reports grants from Action Medical Research, during the conduct of the study; grants from Tommy's, grants from NIHR, outside the submitted work;

Dr. Stacey reports grants from Cure Kids (3537), Nurture Foundation, Auckland District Health Board Charitable Trust., grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., during the conduct of the study;

Professor Askie has nothing to disclose;

Professor Mitchell reports grants from Cure Kids (Grant 3537), Nurture Foundation, Auckland District Health Board Trust., grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), during the conduct of the study; other from Cure Kids, outside the submitted work;

Associate Professor Thompson reports grants from Cure Kids (3537), Nurture Foundation, Auckland District Health Board Charitable Trust., grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), during the conduct of the study;

Professor McCowan reports grants from Cure Kids (537), Nurture Foundation, Auckland District Health Board Trust., grants from Health Research Council of New Zealand (12/372); Cure Kids (5357); Mercia Barnes Trust; Nurture Foundation; University of Auckland Faculty Research Development Fund (3700696)., grants from 2016 TransTasman Red Nose/Curekids (6601), during the conduct of the study.

Associate Professor O'Brien reports grants from American Sleep Medicine Foundation, grants from ResMed, outside the submitted work;

We note that you received funding from a commercial source: ResMed

Please provide an amended Competing Interests Statement that explicitly states this commercial funder, along with any other relevant declarations relating to employment, consultancy, patents, products in development, marketed products, etc.

Within this Competing Interests Statement, please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include your amended Competing Interests Statement within your cover letter. We will change the online submission form on your behalf.

Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests

4. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

Additional Editor Comments:

Only some minor changes have been requested by the Reviewers; please modify the manuscript as requested.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The aim of this work is to find the relationship of symptom of SDB and late stillbirth from previously done case-control studies that is available and pool them together using statistical technique. The point that this paper is a successful collaboration between large teams around the globe combining with a robust individual patient-level data analysis technique is interesting. I congratulate the authors for their efforts.

Overall I find the manuscript to be of good quality, however some minor revision points may need to be done:

1. Study selection process report need to be more transparent, i.e. the authors should describe number of study that were excluded (fig. 1 may need to be revised) how many duplicates were there?, why 124 studies did not meet the eligibility criteria? There should be more detail on the number and reason of studies that were excluded, to provided that the author has established all available evidences to support the meta-analysis. Also, for one study that is not participating, is there any difference in characteristic of that particular study compared to participating studies? (The author may need to describe about this in the result)

2. Case control studies were prone to recall bias and combining case-control in meta-analysis can still be susceptible to this. I wonder if there any other supporting evidences from cohort study? If there is not the author should specifically mention about the result of the assessment of quality of the evidence in the result, and emphasis on the possibility of bias upon making conclusion, which may need a large pregnancy cohort to be done.

Again, I sincerely admire the authors' efforts into the collaborating process.

Reviewer #2: Comments to the Author

-How the duration of overnight sleep was evaluated? Did you use a standardized sleep log?

-How did you evaluated the sleep position (supine and not supine)? Is this data only self-reported? Or did you use some instruments to evaluate it? If only self-reported, it can probably be inaccurate because you can’t know the real position throughout the night. Can you specify it?

-You suggest that a reduction in the odds of late stillbirth for women who reported restless sleep during the last month may be is due to maternal body movement facilitating maternal-fetal blood flow, potentially abating adverse fetal effects of aortocaval compression. Considering that the supine position is associated with an increase in aortocaval compression, have you evaluated interactions between restless sleep and sleep position to understand if the reduced risk of late stillbirth in these cases can be related to the position?

-You report that the combined effect of supine going-to-sleep position and habitual snoring resulted in a reduced odds of late stillbirth in the multivariable model and you explain this result assuming that snoring can cause arousal that can cause a change of position from supine to lateral. It would be interesting to test this hypothesis with an objective assessment of the position.

-You report that getting up to use the toilet in the night is associated with a reduced risk of late stillbirth, suggesting that maternal body movement on the night may mitigate the effects of a hypoxic event on the fetus. Considering that getting up to use the toilet in the night can be also a clinical manifestation of SBD, have you analyzed interactions between the use of the toilet in the night and Berlin Questionnaire (excluding BMI)?

-Non using objective measures (polysomnography) for SBD’s evaluation may be a limitation as you specified. Didn’t you evaluate the possibility to assess the polysomography, if not possibile in all the women, in some of them such as patients with positive Berlin Questionnaire (excluding BMI), in patients with restless sleep and in patients getting up to use the toilet?

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Dott.ssa Francesca Furia

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Mar 26;15(3):e0230861. doi: 10.1371/journal.pone.0230861.r002

Author response to Decision Letter 0

15 Feb 2020

The authors thank the editorial team and reviewers’ for their comments. The manuscript has been revised according to the comments.

EDITORIAL FEEDBACK

1) When submitting your revision, we need you to address these additional requirements.

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

- AUTHOR RESPONSE: We agree, and have addressed these additional requirements.

2) Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information

- AUTHOR RESPONSE: We agree, and have added detail to the captions for the Supporting Information files at the end of our manuscript.

3) Thank you for stating the following in the Financial Disclosure section… We note that you received funding from a commercial source: ResMed. Please provide an amended Competing Interests Statement that explicitly states this commercial funder, along with any other relevant declarations relating to employment, consultancy, patents, products in development, marketed products, etc. Within this Competing Interests Statement, please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include your amended Competing Interests Statement within your cover letter. We will change the online submission form on your behalf.

- AUTHOR RESPONSE: We agree, and have amended our Competing Interests Statement as follows:

“Associate Professor O'Brien reports grants from ResMed outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.”

This amended Competing Interests Statement has been included within our cover letter. Thank you for changing the online submission form on our behalf.

4) We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

We will update your Data Availability statement on your behalf to reflect the information you provide.

- AUTHOR RESPONSE: We have provided additional details regarding the ethical restrictions on sharing our data publicly in our revised cover letter as follows:

“Data cannot be shared publicly beyond the Collaborative Individual Participant Data Meta-analysis of Sleep and Stillbirth (CRIBSS) group as no individual participating study obtained consent from participants to make the data publically available. Furthermore, because stillbirth is uncommon there is potential for participants to be identifiable. Contact information for the CRIBSS Data Access Committee is The CRIBSS Data Centre, Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142.”

Thank you for updating our Data Availability statement.

REVIEWER FEEDBACK

REVIEWER # 1

1.1) The aim of this work is to find the relationship of symptom of SDB and late stillbirth from previously done case-control studies that is available and pool them together using statistical technique. The point that this paper is a successful collaboration between large teams around the globe combining with a robust individual patient-level data analysis technique is interesting. I congratulate the authors for their efforts. Overall I find the manuscript to be of good quality, however some minor revision points may need to be done:

- AUTHOR RESPONSE: Thank you.

1.2) Study selection process report need to be more transparent, i.e. the authors should describe number of study that were excluded (fig. 1 may need to be revised) how many duplicates were there?, why 124 studies did not meet the eligibility criteria? There should be more detail on the number and reason of studies that were excluded, to provided that the author has established all available evidences to support the meta-analysis. Also, for one study that is not participating, is there any difference in characteristic of that particular study compared to participating studies? (The author may need to describe about this in the result)

- AUTHOR RESPONSE: We agree, and have revised “Figure 1 PRISMA study population flow chart,” which now includes the number of duplicate articles, and participant level inclusion and exclusion criteria. We have also added more detail to the Strengths and Limitations section as follows:

“Our search had no language restriction and an eligible study from India was identified, however, there was no response from authors or journal editors to repeated invitations to participate. No other eligible randomised trials, prospective cohort studies or studies from low-income countries were identified, thus participating studies were all case-control studies from high-income countries.”

Please note that a December 23, 2019 update for Beall's List of Predatory Journals and Publishers states that the journal that published the non-participating study from India (the International Journal of Reproduction, Contraception, Obstetrics and Gynecology) has been included with “journals that were not originally on the Beall's list but may be predatory.” https://beallslist.net/standalone-journals/

1.3) Case control studies were prone to recall bias and combining case-control in meta-analysis can still be susceptible to this. I wonder if there any other supporting evidences from cohort study? If there is not the author should specifically mention about the result of the assessment of quality of the evidence in the result, and emphasis on the possibility of bias upon making conclusion, which may need a large pregnancy cohort to be done.

- AUTHOR RESPONSE: We agree that case-control studies have the limitation of recall bias, and that supporting evidence from cohort studies should be reported where available. This has been explained in the Strengths and Limitations section, and we have clarified that that it is the relationship between late stillbirth and maternal sleep that is not universally well known as follows:

“A limitation of case-control studies include the retrospective data collection which is subject to potential recall bias, although as the relationship between late stillbirth and maternal sleep is not universally well known by pregnant women, systematic bias is unlikely. The longer length of time before interview for cases may have influenced their recall compared to controls, however, case recall is unlikely to be biased towards an association with SDB, with self-reports from a single night of sleep having similar bias and calibration as ‘usual’ sleep [70]. Use of self-reported symptoms of SDB, rather than objective measures using polysomnography may also be considered a limitation. However, self-report of snoring is strongly and reliably associated with the severity of OSA obtained from polysomnography in non-pregnant [71] and pregnant women [46]; therefore self-report is useful for large-scale studies where routine access to polysomnography in late pregnancy is costly and impractical.”

We also agree that the assessment of the quality of the evidence should be reported. Under the Materials and Methods section, we have already provided a reference to the risk of bias tool and risk of bias report used for this study as follows:

“This IPD meta-analysis was registered with the PROSPERO register of systematic reviews (CRD42017047703) and followed the IPD meta-analysis protocol [38], search strategy [24], risk of bias for non-randomised studies (ROBINS-E) tool [39], and published results [24].”

REVIEWER #2

2.1) How the duration of overnight sleep was evaluated? Did you use a standardized sleep log?

- AUTHOR RESPONSE: Sleep data, including sleep duration, were collected by self-report in all participating studies. No study collected sleep data via standardised sleep log or actigraphy. To make this clear, we have added the words “self-report” to the Materials and Methods section as follows:

“Maternal sleep data were collected by self-report via face-to-face interview [26, 27, 30, 31] or online survey [32] within six weeks after stillbirth in cases or at a matched gestation in controls”

2.2) a) How did you evaluated the sleep position (supine and not supine)? Is this data only self-reported? Or did you use some instruments to evaluate it? b) If only self-reported, it can probably be inaccurate because you can’t know the real position throughout the night. Can you specify it.

- AUTHOR RESPONSE:

a) Please see answer to 2.1.

b) The participating studies were all questionnaire based, data on maternal sleep position throughout the night was not collected. The supine/non-supine going-to-sleep position variable in our manuscript refers only to going-to-sleep position. The reason that going-to-sleep position was the chosen variable was because this is most easily recalled and modifiable for the majority of women in late pregnancy (Cronin et al., 2017, https://doi.org/10.1186/s12884-017-1378-5). We were not able to validate maternal self-report of going-to-sleep position in the individual studies, however, in some of the participating studies the investigators reported that participants often described reference points to remember their going-to-sleep position, such as facing the door. In addition, McIntyre et al’s 2016 overnight sleep study of 30 healthy women in late pregnancy (https://doi.org/10.1186/s12884-016-0905-0), reported good agreement for going-to-sleep (sleep onset) position between infared digital video and self-completed questionnaires for participants (who were not given any information about sleep position), with the majority accurately recalling their going-to-sleep position.

2.3) You suggest that a reduction in the odds of late stillbirth for women who reported restless sleep during the last month may be is due to maternal body movement facilitating maternal-fetal blood flow, potentially abating adverse fetal effects of aortocaval compression. Considering that the supine position is associated with an increase in aortocaval compression, have you evaluated interactions between restless sleep and sleep position to understand if the reduced risk of late stillbirth in these cases can be related to the position?

- AUTHOR RESPONSE: We agree that the relationship between restless sleep and supine going-to-sleep position is interesting. Therefore, we have added the analysis of interaction between supine going-to-sleep position and restless sleep greater than average last month to “Table 3: Analysis for interaction between supine going-to-sleep position, and habitual snoring, the Berlin Questionnaire, sleep duration >9 hours and restless sleep greater than average.” The interaction between supine going-to-sleep position and restless sleep was not statistically significant (p=0.98).

2.4) You report that the combined effect of supine going-to-sleep position and habitual snoring resulted in a reduced odds of late stillbirth in the multivariable model and you explain this result assuming that snoring can cause arousal that can cause a change of position from supine to lateral. It would be interesting to test this hypothesis with an objective assessment of the position.

- AUTHOR RESPONSE: We agree that an objective assessment of sleep position in women with habitual snoring during late pregnancy would be of great interest and could be evaluated in future studies.

2.5) You report that getting up to use the toilet in the night is associated with a reduced risk of late stillbirth, suggesting that maternal body movement on the night may mitigate the effects of a hypoxic event on the fetus. Considering that getting up to use the toilet in the night can be also a clinical manifestation of SBD, have you analyzed interactions between the use of the toilet in the night and Berlin Questionnaire (excluding BMI)?

- AUTHOR RESPONSE: We agree that we reported that getting up to use the toilet on the night before stillbirth was associated with halving of the odds of late stillbirth in three individual studies. However, there was no association found between getting up to use the toilet during the month before stillbirth in the analysis reported in our manuscript.

2.6) Non using objective measures (polysomnography) for SBD’s evaluation may be a limitation as you specified. Didn’t you evaluate the possibility to assess the polysomography, if not possibile in all the women, in some of them such as patients with positive Berlin Questionnaire (excluding BMI), in patients with restless sleep and in patients getting up to use the toilet?

- AUTHOR RESPONSE: The participating studies were all questionnaire based and any referral for polysomnography was not captured.

PLoS One. doi: 10.1371/journal.pone.0230861.r003

Decision Letter 1

Claudio Liguori

11 Mar 2020

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

PONE-D-19-22011R1

Dear Dr. Cronin,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

With kind regards,

Claudio Liguori

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: Yes

**********

6. Review Comments to the Author

Reviewer #2: I congratulate the authors for their work. I find that the manuscript is well written, well analizyzed and of good quality.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: Francesca Furia

PLoS One. doi: 10.1371/journal.pone.0230861.r004

Acceptance letter

Claudio Liguori

13 Mar 2020

PONE-D-19-22011R1

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

Dear Dr. Cronin:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

For any other questions or concerns, please email plosone@plos.org.

Thank you for submitting your work to PLOS ONE.

With kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Claudio Liguori

Academic Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Fig. Chart of available data from contributing studies.

(DOCX)

Click here for additional data file.^{(93.5KB, docx)}

S1 Table. Participant level characteristics and non-sleep late stillbirth risk factors in participating case-control studies and pooled IPD meta-analysis.

(DOCX)

Click here for additional data file.^{(32.5KB, docx)}

S1 Checklist. PRISMA-P (Preferred reporting items for systematic review and meta-analysis protocols) 2015 checklist: Recommended items to address in a systematic review protocol*.

(DOC)

Click here for additional data file.^{(82KB, doc)}

S1 Protocol

(PDF)

Click here for additional data file.^{(355.6KB, pdf)}

Data Availability Statement

[pone.0230861.ref001] 1.Heazell A, Siassakos D, Blencowe H, Burden C, Bhutta Z, Cacciatore J, et al. Stillbirths: economic and psychosocial consequences. Lancet. 2016;387(10018):604–16. 10.1016/S0140-6736(15)00836-3 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref002] 2.Reinebrant HE, Leisher SH, Coory M, Henry S, Wojcieszek AM, Gardener G, et al. Making stillbirths visible: a systematic review of globally reported causes of stillbirth. BJOG: An International Journal of Obstetrics & Gynaecology. 2017. [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref003] 3.Flenady V, Wojcieszek A, Middleton P, Ellwood D, Erwich J, Coory M, et al. Stillbirths: Recall to action in high-income countries. Lancet. 2016;387:691–702. 10.1016/S0140-6736(15)01020-X [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref004] 4.O’Brien LM, Bullough AS, Owusu JT, Tremblay KA, Brincat CA, Chames MC, et al. Pregnancy-onset habitual snoring, gestational hypertension, and preeclampsia: prospective cohort study. Am J Obstet Gynecol. 2012;207(6):487.e1–.e9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref005] 5.Bourjeily G, Raker C, Chalhoub M, Miller M. Pregnancy and fetal outcomes of symptoms of sleep-disordered breathing. Eur Respir J. 2010;36(4):849–55. 10.1183/09031936.00021810 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref006] 6.Izci B, Martin SE, Dundas KC, Liston WA, Calder AA, Douglas NJ. Sleep complaints: snoring and daytime sleepiness in pregnant and pre-eclamptic women. Sleep Med. 2005;6(2):163–9. 10.1016/j.sleep.2004.12.007 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref007] 7.Facco FL, Parker CB, Reddy UM, Silver RM, Koch MA, Louis JM, et al. Association between sleep-disordered breathing and hypertensive disorders of pregnancy and gestational diabetes mellitus. Obstet Gynecol. 2017;129(1):31 10.1097/AOG.0000000000001805 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref008] 8.Pien GW, Pack AI, Jackson N, Maislin G, Macones GA, Schwab RJ. Risk factors for sleep-disordered breathing in pregnancy. Thorax. 2013:thoraxjnl-2012-202718. [DOI] [PMC free article] [PubMed]

[pone.0230861.ref009] 9.Bin YS, Cistulli PA, Ford JB. Population-based study of sleep apnea in pregnancy and maternal and infant outcomes. J Clin Sleep Med. 2016;12(06):871–7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref010] 10.Williams MA, Miller RS, Qiu C, Cripe SM, Gelaye B, Enquobahrie D. Associations of early pregnancy sleep duration with trimester-specific blood pressures and hypertensive disorders in pregnancy. Sleep. 2010;33(10):1363–71. 10.1093/sleep/33.10.1363 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref011] 11.Facco FL, Grobman WA, Kramer J, Ho KH, Zee PC. Self-reported short sleep duration and frequent snoring in pregnancy: impact on glucose metabolism. Am J Obstet Gynecol. 2010;203(2):142.e1–.e5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref012] 12.Qiu C, Enquobahrie D, Frederick IO, Abetew D, Williams MA. Glucose intolerance and gestational diabetes risk in relation to sleep duration and snoring during pregnancy: a pilot study. BMC Womens Health. 2010;10(1):17. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref013] 13.Reutrakul S, Zaidi N, Wroblewski K, Kay HH, Ismail M, Ehrmann DA, et al. Sleep disturbances and their relationship to glucose tolerance in pregnancy. Diabetes Care. 2011;34(11):2454–7. 10.2337/dc11-0780 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref014] 14.Micheli K, Komninos I, Bagkeris E, Roumeliotaki T, Koutis A, Kogevinas M, et al. Sleep patterns in late pregnancy and risk of preterm birth and fetal growth restriction. Epidemiology. 2011:738–44. 10.1097/EDE.0b013e31822546fd [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref015] 15.Abeysena C, Jayawardana P, Seneviratne RDA. Maternal sleep deprivation is a risk factor for small for gestational age: a cohort study. Aust N Z J Obstet Gynaecol. 2009;49(4):382–7. 10.1111/j.1479-828X.2009.01010.x [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref016] 16.Fung AM, Wilson DL, Lappas M, Howard M, Barnes M, O’Donoghue F, et al. Effects of maternal obstructive sleep apnoea on fetal growth: a prospective cohort study. PLoS One. 2013;8(7):e68057 10.1371/journal.pone.0068057 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref017] 17.Pamidi S, Marc I, Simoneau G, Lavigne L, Olha A, Benedetti A, et al. Maternal sleep-disordered breathing and the risk of delivering small for gestational age infants: a prospective cohort study. Thorax. 2016;71(8):719–25. 10.1136/thoraxjnl-2015-208038 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref018] 18.O’Brien LM, Bullough AS, Owusu JT, Tremblay KA, Brincat CA, Chames MC, et al. Snoring during pregnancy and delivery outcomes: a cohort study. Sleep. 2013;36(11):1625–32. 10.5665/sleep.3112 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref019] 19.Kneitel AW, Treadwell MC, O’Brien LM. Effects of maternal obstructive sleep apnea on fetal growth: a case-control study. J Perinatol. 2018;38(8):982 10.1038/s41372-018-0127-6 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref020] 20.Li R, Zhang J, Zhou R, Liu J, Dai Z, Liu D, et al. Sleep disturbances during pregnancy are associated with cesarean delivery and preterm birth. J Matern-Fetal Neonatal Med. 2017;30(6):733–8. 10.1080/14767058.2016.1183637 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref021] 21.Kajeepeta S, Sanchez SE, Gelaye B, Qiu C, Barrios YV, Enquobahrie DA, et al. Sleep duration, vital exhaustion, and odds of spontaneous preterm birth: a case-control study. BMC Pregnancy Childbirth. 2014;14:337 10.1186/1471-2393-14-337 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref022] 22.Dunietz GL, Shedden K, Schisterman EF, Lisabeth LD, Treadwell MC, O’Brien LM. Associations of snoring frequency and intensity in pregnancy with time-to-delivery. Paediatr Perinat Epidemiol. 2018;32(6):504–11. 10.1111/ppe.12511 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref023] 23.Ura M, Fujimoto K. Relationship between sleep-disordered breathing and sleeping position at the 37th week of pregnancy: an observational cross-sectional study. Sleep Biol Rhythms. 2018;16(4):441–7. [Google Scholar]

[pone.0230861.ref024] 24.Cronin RS, Li M, Thompson JMD, Gordon A, Raynes-Greenow CH, Heazell AEP, et al. An Individual Participant Data Meta-analysis of Maternal Going-to-Sleep Position, Interactions with Fetal Vulnerability, and the Risk of Late Stillbirth. EClinicalMedicine. 2019;10:49–57. 10.1016/j.eclinm.2019.03.014 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref025] 25.Warland J, Dorrian J, Morrison JL, O’Brien LM. Maternal sleep during pregnancy and poor fetal outcomes: A scoping review of the literature with meta-analysis. Sleep Med Rev. 2018;41:197–219. 10.1016/j.smrv.2018.03.004 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref026] 26.Stacey T, Thompson J, Mitchell EA, Ekeroma AJ, Zuccollo JM, McCowan LM. Association between maternal sleep practices and risk of late stillbirth: a case-control study. BMJ. 2011;342:d3403 10.1136/bmj.d3403 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref027] 27.Gordon A, Raynes-Greenow C, Bond D, Morris J, Rawlinson W, Jeffery H. Sleep position, fetal growth restriction, and late-pregnancy stillbirth: the Sydney stillbirth study. Obstet Gynecol. 2015;125:347–55. 10.1097/AOG.0000000000000627 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref028] 28.Louis J, Auckley D, Miladinovic B, Shepherd A, Mencin P, Kumar D, et al. Perinatal outcomes associated with obstructive sleep apnea in obese pregnant women. Obstet Gynecol. 2012;120(5). [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref029] 29.Louis JM, Mogos MF, Salemi JL, Redline S, Salihu HM. Obstructive sleep apnea and severe maternal-infant morbidity/mortality in the United States, 1998–2009. Sleep. 2014;37(5):843–9. 10.5665/sleep.3644 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref030] 30.Heazell A, Li M, Budd J, Thompson J, Stacey T, Cronin R, et al. Association between maternal sleep practices and late stillbirth–findings from a stillbirth case-control study. BJOG. 2017;125:254–62. 10.1111/1471-0528.14967 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref031] 31.McCowan L, Thompson J, Cronin R, Li M, Stacey T, Stone P, et al. Going to sleep in the supine position is a modifiable risk factor for late pregnancy stillbirth; Findings from the New Zealand multicentre stillbirth case-control study. PLoS One. 2017;12:e0179396 10.1371/journal.pone.0179396 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref032] 32.O’Brien LM, Warland J, Stacey T, Heazell AE, Mitchell EA, on behalf of the STARS Consortium. Maternal sleep practices and stillbirth: Findings from an international case-control study. Birth. 2019:1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref033] 33.Owusu JT, Anderson FJ, Coleman J, Oppong S, Seffah JD, Aikins A, et al. Association of maternal sleep practices with pre-eclampsia, low birth weight, and stillbirth among Ghanaian women. Int J Gynaecol Obstet. 2013;121:261–5. 10.1016/j.ijgo.2013.01.013 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref034] 34.Warland J, Mitchell EA. A triple risk model for unexplained late stillbirth. BMC Pregnancy Childbirth. 2014;14:142 10.1186/1471-2393-14-142 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref035] 35.Izci-Balserak B, Pien GW. Sleep-disordered breathing and pregnancy: potential mechanisms and evidence for maternal and fetal morbidity. Curr Opin Pulm Med. 2010;16(6):574 10.1097/MCP.0b013e32833f0d55 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref036] 36.Kerr M, Scott D, Samuel E. Studies of the inferior vena cava in late pregnancy. BMJ. 1964;1:522–4. [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref037] 37.Humphries A, Ali Mirjalili S, Tarr GP, Thompson JM, Stone P. The effect of supine positioning on maternal hemodynamics during late pregnancy. The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2018:1–8. [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref038] 38.Li M, Thompson JM, Cronin RS, Gordon A, Raynes-Greenow C, Heazell AE, et al. The Collaborative IPD of Sleep and Stillbirth (Cribss): is maternal going-to-sleep position a risk factor for late stillbirth and does maternal sleep position interact with fetal vulnerability? An individual participant data meta-analysis study protocol. BMJ Open. 2018;8:e020323 10.1136/bmjopen-2017-020323 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref039] 39.Morgan R. The ROBINS-E tool (Risk Of Bias In Non-randomized Studies—of Exposures) [Internet]: University of Bristol; 2017. [https://www.bristol.ac.uk/population-health-sciences/centres/cresyda/barr/riskofbias/robins-e/ [Google Scholar]

[pone.0230861.ref040] 40.World Health Organization. Neonatal and perinatal mortality for the year 2000: country, regional and global estimates [Internet] Geneva: World Health Organization; 2006. [http://whqlibdoc.who.int/publications/2006/9241563206_eng.pdf [Google Scholar]

[pone.0230861.ref041] 41.Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the berlin questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med. 1999;131(7):485–91. 10.7326/0003-4819-131-7-199910050-00002 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref042] 42.Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14. [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref043] 43.Franklin KA, Holmgren PA, Jonsson F, Poromaa N, Stenlund H, Svanborg E. Snoring, pregnancy-induced hypertension, and growth retardation of the fetus. Chest. 2000;117(1):137–41. 10.1378/chest.117.1.137 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref044] 44.Ursavas A, Karadag M, Nalcı N, Ercan I, Gozu RO. Self-reported snoring, maternal obesity and neck circumference as risk factors for pregnancy-induced hypertension and preeclampsia. Respiration. 2007;76(1):33–9. 10.1159/000107735 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref045] 45.Hutchison B, Stone P, McCowan L, Stewart A, Thompson J, Mitchell E. A postal survey of maternal sleep in late pregnancy. BMC Pregnancy Childbirth. 2012;12. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref046] 46.Louis JM, Koch MA, Reddy UM, Silver RM, Parker CB, Facco FL, et al. Predictors of sleep-disordered breathing in pregnancy. Am J Obstet Gynecol. 2018;218(5):521.e1–.e12. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref047] 47.Tantrakul V, Numthavaj P, Guilleminault C, McEvoy M, Panburana P, Khaing W, et al. Performance of screening questionnaires for obstructive sleep apnea during pregnancy: A systematic review and meta-analysis. Sleep Med Rev. 2016. [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref048] 48.Antony KM, Agrawal A, Arndt ME, Murphy AM, Alapat PM, Guntupalli KK, et al. Association of Adverse Perinatal Outcomes with Screening Measures of Obstructive Sleep Apnea. Am J Perinatol. 2011;28(8):651–8. [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref049] 49.O’Brien LM, Levine R, Dunietz GL, Bullough AS, Chames MC, MC T. Use of the Berlin Questionnaire in Pregnancy Primarily Identifies Obesity Not Sleep-Disordered Breathing. Under review. 2019.

[pone.0230861.ref050] 50.Signal TL, Paine S-J, Sweeney B, Priston M, Muller D, Smith A, et al. Prevalence of abnormal sleep duration and excessive daytime sleepiness in pregnancy and the role of socio-demographic factors: comparing pregnant women with women in the general population. Sleep Med. 2014;15(12):1477–83. 10.1016/j.sleep.2014.07.007 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref051] 51.Ladyman C, Signal TL. Sleep health in pregnancy: a scoping review. Sleep Med Clin. 2018;13(3):307–33. 10.1016/j.jsmc.2018.04.004 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref052] 52.McIntyre J, Ingham C, Hutchinson B, Thompson J, McCowan L, Stone P, et al. A description of sleep behaviour in healthy late pregnancy, and the accuracy of self-reports. BMC Pregnancy Childbirth. 2016;16:1–8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref053] 53.Beebe KR, Lee KA. Sleep disturbance in late pregnancy and early labor. The Journal of perinatal & neonatal nursing. 2007;21(2):103–8. [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref054] 54.Taylor RS, Gamble G, McCowan L, North RA. Sleep effects on ambulatory blood pressure measurements in pregnant women. Am J Hypertens. 2001;14(1):38–43. 10.1016/s0895-7061(00)01226-7 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref055] 55.Jeffreys R, Stepanchak W, Lopez B, Hardis J, Clapp J. Uterine blood flow during supine rest and exercise after 28 weeks of gestation. BJOG. 2006;113:1239–47. 10.1111/j.1471-0528.2006.01056.x [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref056] 56.Steer PJ, Little MP, Kold-Jensen T, Chapple J, Elliott P. Maternal blood pressure in pregnancy, birth weight, and perinatal mortality in first births: prospective study. BMJ. 2004;329(7478):1312 10.1136/bmj.38258.566262.7C [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref057] 57.Ng PH, Walters WAW. The effects of chronic maternal hypotension during pregnancy. Aust N Z J Obstet Gynaecol. 1992;32(1):14–6. 10.1111/j.1479-828x.1992.tb01888.x [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref058] 58.Friedman EA, Neff RK. Hypertension-Hypotension in Pregnancy: Correlation With Fetal Outcome. JAMA. 1978;239(21):2249–51. [PubMed] [Google Scholar]

[pone.0230861.ref059] 59.Warland J, McCutcheon H, Baghurst P. Maternal blood pressure in pregnancy and stillbirth: a case-control study of third-trimester stillbirth. Am J Perinatol. 2008;25(05):311–7. [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref060] 60.Wilson DL, Barnes M, Ellett L, Permezel M, Jackson M, Crowe SF. Decreased sleep efficiency, increased wake after sleep onset and increased cortical arousals in late pregnancy. Aust N Z J Obstet Gynaecol. 2011;51(1):38–46. 10.1111/j.1479-828X.2010.01252.x [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref061] 61.Javaheri S, Redline S. Sleep, slow-wave sleep, and blood pressure. Curr Hypertens Rep. 2012;14(5):442–8. 10.1007/s11906-012-0289-0 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref062] 62.Thurlow J, Kinsella S. Intrauterine resuscitation: active management of fetal distress. Int J Obstet Anesth. 2002;11(2):105–16. 10.1054/ijoa.2001.0933 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref063] 63.Pien GW, Schwab RJ. Sleep disorders during pregnancy. Sleep. 2004;27:1405–17. 10.1093/sleep/27.7.1405 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref064] 64.Okun ML, Roberts JM, Marsland AL, Hall M. How disturbed sleep may be a risk factor for adverse pregnancy outcomes. Obstet Gynecol Surv. 2009;64(4):273–80. 10.1097/OGX.0b013e318195160e [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref065] 65.Robertson N, Turner J, Kumar S. Pathophysiological changes associated with sleep disordered breathing and supine sleep position in pregnancy. Sleep Med Rev. 2019;46:1–8. 10.1016/j.smrv.2019.04.006 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref066] 66.Hegewald MJ, Crapo RO. Respiratory physiology in pregnancy. Clin Chest Med. 2011;32(1):1–13. 10.1016/j.ccm.2010.11.001 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref067] 67.Brownell L, West P, Kryger M. Breathing during Sleep in Normal Pregnant Women 1–3. Am Rev Respir Dis. 1986;133(1):38–41. 10.1164/arrd.1986.133.1.38 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref068] 68.Driver HS, Shapiro CM. A Longitudinal Study of Sleep Stages in Young Women During Pregnancy and Postpartum. Sleep. 1992;15(5):449–53. 10.1093/sleep/15.5.449 [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref069] 69.Mills G, Chaffe A. Sleeping positions adopted by pregnant women of more than 30 weeks gestation. Anaesthesia. 1994;49(3):249–50. 10.1111/j.1365-2044.1994.tb03433.x [DOI] [PubMed] [Google Scholar]

[pone.0230861.ref070] 70.Lauderdale DS, Knutson KL, Yan LL, Liu K, Rathouz PJ. Sleep duration: how well do self-reports reflect objective measures? The CARDIA Sleep Study. Epidemiology. 2008;19(6):838–45. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0230861.ref071] 71.Bliwise DL, Nekich JC, Dement WC. Relative validity of self-reported snoring as a symptom of sleep apnea in a sleep clinic population. Chest. 1991;99(3):600–8. [DOI] [PubMed] [Google Scholar]

PERMALINK

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

Robin S Cronin

Jessica Wilson

Adrienne Gordon

Minglan Li

Vicki M Culling

Camille H Raynes-Greenow

Alexander E P Heazell

Tomasina Stacey

Lisa M Askie

Edwin A Mitchell

John M D Thompson

Lesley M E McCowan

Louise M O’Brien

Roles

Abstract

Background and objectives

Methods

Results

Conclusion

Introduction

Materials and methods

Data analysis

Table 1. Study level characteristics and measured sleep-related factors in participating studies.

Results

Fig 1. PRISMA study population flow chart.

Table 2. Subjective indicators of sleep-disordered breathing and maternal sleep patterns in participating case-control studies and pooled IPD meta-analysis.

Fig 2. Women who had a stillbirth and their perception of timing of the death.

Table 3. Analysis for interaction between supine going-to-sleep position, and habitual snoring, the Berlin Questionnaire, sleep duration >9 hours and restless sleep greater than average.

Discussion

Main findings

Strengths and limitations

Conclusion

Supporting information

Acknowledgments

Data Availability

Funding Statement

References

Decision Letter 0

Claudio Liguori

Roles

Author response to Decision Letter 0

Decision Letter 1

Claudio Liguori

Roles

Acceptance letter

Claudio Liguori

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases