Survey of maternal sleep practices in late pregnancy in a multi-ethnic sample in South Auckland, New Zealand

Robin S Cronin
Carol Chelimo
Edwin A Mitchell
Kara Okesene-Gafa
John M D Thompson
Rennae S Taylor
B Lynne Hutchison
Lesley M E Mccowan
Survey of maternal sleep practices in late pregnancy in a multi-ethnic sample in South Auckland, New Zealand
10.1186/s12884-017-1378-5R E S E A R C H A R T I C L E Open Access
Background:The Auckland Stillbirth study demonstrated a two-fold increased risk of late stillbirth for women who did not go to sleep on their left side. Two further studies have confirmed an increased risk of late stillbirth with supine sleep position. As sleep position is modifiable, we surveyed self-reported late pregnancy sleep position, knowledge about sleep position, and views about changing going-to-sleep position. Methods: Participants in this 2014 survey were pregnant women (n = 377) in their third trimester from South Auckland, New Zealand, a multi-ethnic and predominantly low socio-economic population. An ethnicallyrepresentative sample was obtained using random sampling. Multivariable logistic regression was performed to identify factors independently associated with non-left sided going-to-sleep position in late pregnancy. Results: Respondents were 28 to 42 weeks' gestation. Reported going-to-sleep position in the last week was left side (30%), right side (22%), supine (3%), either side (39%) and other (6%). Two thirds (68%) reported they had received advice about sleep position. Non-left sleepers were asked if they would be able to change to their left side if it was better for their baby; 87% reported they would have little or no difficulty changing. Women who reported a non-left going-to-sleep position were more likely to be of Maori (aOR 2.64 95% CI 1.23-5.66) or Pacific (aOR 2.91 95% CI 1.46-5.78) ethnicity; had a lower body mass index (BMI) (aOR 0.93 95% CI 0.89-0.96); and were less likely to sleep on the left-hand side of the bed (aOR 3.29 95% CI 2.03-5.32). Conclusions: Maternal going-to-sleep position in the last week was side-lying in 91% of participants. The majority had received advice to sleep on their side or avoid supine sleep position. Sleeping on the left-hand side of the bed was associated with going-to-sleep on the left side. Most non-left sleepers reported their sleeping position could be modified to the left side suggesting a public health intervention about sleep position is likely to be feasible in other multi-ethnic communities.

Background

Maternal sleep position in late pregnancy may be a modifiable risk factor for late stillbirth (≥28 weeks) [1]. In the Auckland Stillbirth Study, a matched case control study, women who did not go to sleep on their left side the night before the stillbirth was thought to have occurred, were twice as likely to have a late stillbirth compared with those who went to sleep on their left (adjusted odds ratio (aOR) 2.03 95% confidence interval (CI) 1.24-3.29) [1]. Supine going-to-sleep position was associated with the highest rate of late stillbirth (aOR 2.54 95% CI 1.04-6.18). These findings were independent of other known stillbirth risk factors such as obesity, smoking, and advanced maternal age.

The importance of maternal sleep position and risk of late stillbirth has been confirmed by two subsequent studies [2,3]. The Sydney Stillbirth Study [3], a matched case control study, reported that women who slept on their backs in the preceding month were six times more likely to have a late stillbirth (aOR 6.26 95% CI 1. . Similarly, a cross-sectional survey of maternal sleep practices and adverse pregnancy outcomes, undertaken in 220 recently delivered women in Ghana [2], reported that supine sleep position during pregnancy was associated with an eight-fold increased odds of stillbirth (OR 8.0 95% CI 1. 5-43.2). In addition, interim analysis data from a New Zealand wide case control study of risk factors for late stillbirth reported that the population attributable risk of supine sleep position for late stillbirth was 8.8% [4].

These findings are biologically plausible as supine maternal position in late pregnancy has been associated with decreased maternal cardiac output [5] and uterine perfusion [6,7], compared with left sided maternal position. In addition sleep disturbed breathing is in general more severe in the supine position [8] and in those with obesity [9], which is also an independent risk factor for late stillbirth [10]. Maternal supine position has also been associated with lower fetal oxygen saturation [11] and changes in fetal cerebral blood flow suggestive of hypoxia [12]. It has therefore been hypothesised that maternal supine sleep position in late pregnancy may be the final stressor leading to stillbirth in vulnerable fetuses with other risk factors [13].

In the Auckland Stillbirth Study, 31% of women in the control group with ongoing pregnancies reported left sided going-to-sleep position on the previous night [1]. More recently, the New Zealand wide case control study has reported that left sided sleep position has almost doubled in the last 3 years to 58%. This suggests that pregnant women are receiving information about optimum sleep position in pregnancy and making changes.

Rates of stillbirth in New Zealand are highest in regions with high deprivation [14]; however, there are no data about maternal knowledge regarding sleep position in these communities. Acquisition of such data will provide important information to assist in developing public health interventions aimed at optimising going-to-sleep position in late pregnancy. Therefore, we undertook a survey of sleep practices and knowledge in a representative multi-ethnic sample of pregnant women residing in Counties Manukau Health (a region predominantly of low socio-economic status) in South Auckland, New Zealand [14]. The aims were to investigate: 1) selfreported maternal sleep position in late pregnancy; 2) knowledge about optimal sleep position; 3) sleep practices; and 4) whether pregnant women believed their going-to-sleep position could be changed to the left side if this was identified as being best for the baby's health. We also assessed factors related to non-left going-tosleep position in late pregnancy. We hypothesised that women who slept on the left-hand side of the bed or had received information about sleep position would be more likely to report a left side going-to-sleep position.

Methods

Recruitment and data collection

Participants were pregnant women with a singleton pregnancy at ≥28 weeks' gestation attending communitybased antenatal clinics in South Auckland. Eligible women were recruited by research assistants who obtained verbal consent. The self-administered, 30 question survey was undertaken using an online survey software tool, SurveyMonkey® on an electronic tablet and took 10-15 min to complete. The questionnaire is available as supplementary material (Additional file 1). Ethical approval was provided by the University of Auckland Human Participants Ethics Committee (reference number 011116).

Measures

Maternal demographic data collected included: maternal age, self-identified prioritised ethnicity, country of birth, height and weight, parity, cohabitation with a partner, and the number of people residing in the home. Gestational age on the day of the survey was calculated from the woman's due date recorded in her maternity record. Prioritised ethnicity was reported according to Ministry of Health Protocols [15].

Weight and height were measured by a research assistant or midwife at the time of interview (87.5%, n = 330) and if this information was not available self-reported weight and height were used (12.5%, n = 47). Maternal body mass index (BMI) was calculated (weight (kg)/ height (m) 2 ) and classified according to conventional World Health Organisation [16] criteria. Only two women were classified as underweight with BMI <18.5 kg/m 2 .

Participants were asked what position they usually went to sleep in (over the last week), the reason for their choice of going-to-sleep position, and whether they had received any advice or information about sleep position in late pregnancy. Further questions enquired about the sleep environment: bed size, whether others shared the bed, which side of the bed women usually went to sleep on and why. Women were also asked, "If it was shown that going-to-sleep on your left side in late pregnancy is better for the health of your baby would it be possible for you to change?"

Power calculation and statistical analysis

In order to recruit a representative sample of women in late pregnancy from the Counties Manukau region with at least 50 women from each main ethnic group (Samoan, Tongan, Maori, Asian, New Zealand European, and Other Ethnicity), a sample size of at least 300 was estimated to be required. Descriptive statistics were used to summarise data such as, demographic characteristics, and sleep position and sleep knowledge in late pregnancy. Multivariate logistic regression was performed to identify factors independently associated with non-left sided going-to-sleep position in late pregnancy. Statistical significance was defined at the 5% level. Analysis was carried out using SAS version 9.3 (SAS Institute Inc., Cary, NC, USA).

Results

In total, 398 women participated in the study. Of these, 21 women were excluded from the analysis; 18 respondents were less than 28 weeks of gestation and a further three women did not complete most of the survey. Of the 377 completed surveys, height was not recorded for two women, leaving 375 surveys available for multivariable analysis.

Participants had a median age of 27 (SD = 5.5) years and median gestation of 35.7 (SD = 3.5) weeks. The main ethnic groups were Maori, 23.1% (n = 87); New Zealand European, 19.6% (n = 74); Samoan, 18.3% (n = 69); Tongan, 14.1% (n = 53); Asian, 14.1% (n = 53); Other Ethnicity 10.9% (n = 41). Most were born in New Zealand (71.1%, n = 268) and lived with a partner (81.4%, n = 307). Approximately one quarter (n = 100) had no previous children, while 29.4% (n = 111) had seven or more people residing in the home. Two-thirds (n = 249) of women had a BMI ≥ to 30 at recruitment.

Many participants (61.3%) slept in a queen-size bed and 88.1% reported that they had shared the bed with another person in the last week (Table 1). Similar proportions of women slept on the left-hand (42.4%) and right-hand side of the bed (38.5%). This choice of side of bed was primarily to facilitate getting in and out of bed (39.0%), comfort (35.5%), and habit (32.9%). Almost all (98.1%) women used one or more pillows under their head. The majority (60.5%) reported additional pillows to support their body: 31.6% under their abdomen, 29.2% behind their back, and 25.5% placed a pillow between their knees.

The majority (90.7%) reported that they usually went to sleep on their side (left, right or either side) in the last week. The going-to-sleep position was chosen predominantly for comfort (68.7%). Bed sharing with a partner or children was found to have little (3.7 and 5.3% respectively) influence on the reason for sleep position.

Advice from a doctor or midwife about sleep position in late pregnancy was reported by 64.5%. Over half (53.8%) of the 377 women had been advised to sleep on their side or to avoid sleeping supine. Only 50 Recommended position 15 (4.0) a Percentages add up to more than 100% as some selected more than one reason (13.3%) women recalled being specifically told to sleep on their left side. Other sources of pregnancy sleep position advice were reported by half the women (50.1%) and this advice was similar to that given by a doctor or midwife. Family and friends were the major source (27.3%), followed by the internet (12.5%), books and pamphlets (8.0%), and childbirth educators (5.8%). Advice accessed from mobile phone applications, radio, TV and newspapers was uncommon (2.4%).

Of the 258 women who had received advice, 12.7% (n = 48) changed their going-to-sleep position based on this, including 10 women who were supine sleepers. Thirty five of the 48 women (72.9%) reported they changed to their left side; 54.3% changing from their right side to their left. Five women moved to a propped position and eight to their right side. Most (91.6%) of the 48 women who modified their going-tosleep position based on advice, reported little or no difficulty making this change.

We asked the 263 non-left side sleepers if it would be possible to modify their going-to-sleep position to their left side if this was of benefit to the baby; most (86.3%) responded that they could change with minimal difficulty ( Table 2). Only 5.3% reported that the change would be quite or very difficult. Pillows behind the back (35.3%), between the knees (17.8%), and under the abdomen (11.9%) were considered as potentially helpful aids for over half (59.4%) of the 227 women who reported that change was possible. However, 36 women (13.7% of the non-left side sleepers) reported it would not be possible for them to go to sleep on their left side, even if this was better for the baby; the majority (55.5%) of these women were sleeping on their right side and two (5.6%) reported a supine position.

We also asked about the possibility of changing the side of the bed that women slept on if it would help them change to a left side going-to-sleep position. Of the 217 women who did not usually sleep on the lefthand side of the bed, 83.9% reported that changing to the left-hand side of the bed would be possible.

In the multivariable analysis, four factors were significantly associated with reporting a non-left side going-tosleep position in late pregnancy (Table 3). These were: Maori (aOR 2.64 95% CI 1.23-5.66) and Pacific (aOR 2.91 95% CI 1.46-5.78) ethnicity compared to Asian and predominantly New Zealand European women; lower BMI (aOR 0.93 95% CI 0.89-0.96); and not sleeping on the left-hand side of the bed (aOR 3.29 95% CI 2.03-5.32). Maternal age, gestational age, living with a partner, and receiving advice on pregnancy sleep position from any source were unrelated to non-left side going-to-sleep position.

Discussion

Our survey conducted in a multi-ethnic sample of women in late pregnancy from South Auckland, New Zealand, provides new information about maternal selfreported sleep position, knowledge about optimal sleep position, and whether women could change to a left side going-to-sleep position if there were health benefits for the baby. The large majority (91%) reported that their usual going-to-sleep position in the last week was sidelying. Despite no formal public health education on sleep position in pregnancy, the majority (62%) of participants had received some advice to sleep on their side and to avoid a supine position.

Previous smaller studies [17,18] have reported that women spend more time sleeping on their left side in late pregnancy than non-pregnant women and that left sided sleeping increases as the pregnancy progresses  Percentages add up to more than 100% as some selected more than one reason [18,19]. This may be due to the abdominal distention of advancing pregnancy causing previous sleep positions to become uncomfortable. Indeed, the majority of women in our survey (69%) chose their going-tosleep position in the third trimester because of comfort. In our survey, women reported receiving advice from a doctor or midwife (65%) or media sources (50%) about avoiding supine sleep position or to sleep on their side. Many respondents were therefore aware of the importance of sleep position in late pregnancy. The awareness may be a result of media reports regarding the association of stillbirth and supine sleep following publication of the Auckland Stillbirth Study [1] in conjunction with decades of information about potential consequences of aortocaval compression in the supine position in late pregnancy [5,6]; especially where there is concern for fetal wellbeing [20,21], during epidural induction [22], and caesarean section [23]. Furthermore, despite the reported informality and inconsistency of sleep position advice in late pregnancy, 10 participants had changed from the supine going-to-sleep position to a non-supine position based on advice; the majority moving to left side sleeping with relative ease. Although the absolute risk of stillbirths with supine sleep position is relatively low [1], it is possible that a decrease in supine sleep and increase in left sided sleep position in late pregnancy may be a contributing factor to the significant reduction in unexplained stillbirth at term recently reported in New Zealand [14].

We asked women if they could change their going-tosleep position to their left side if there were health benefits for the baby. Of the 70% who did not currently settle to sleep on their left side, 86% said they could change to left. The large majority (94%) of these women reported that changing would not be difficult for them.

Consistent with findings from another study [18], over half (60%) of participants in our survey reported that they used pillows to support their back, knees and abdomen in their usual going-to-sleep position. Pillows were also the favoured (60%) response when women were asked what might assist those who usually went to sleep in the non-left position to change to their left side, if that was recommended.

Women were asked to identify what side of the bed they usually went to sleep on in the last week. The left-hand side and right-hand side were similar (42 and 39% respectively), followed by middle (10%) and unsure (10%). These figures differed somewhat from an Australian study [18] of 30 women where a greater (57%) proportion reported sleeping on the right-hand side of the bed, less (37%) on the left-hand side, and 7% slept in a single bed. We undertook multivariable analysis to identify risk factors associated with non-left side going-to-sleep position. The non-modifiable risk factor of ethnicity was identified, which may enable targeting of a future public health intervention on sleep position. BMI was also identified as a risk factor, with heavier women being more likely to sleep on the left side, a finding we are not currently able to explain. A novel and modifiable factor that could become incorporated into a late pregnancy sleep routine, was that sleeping on the left-hand side of bed is associated with a left side going-to-sleep position. Encouragingly, the large majority of participants (84%) who did not currently sleep on the left-hand side of the bed reported that they could change the side of bed they slept on, to help to modify their usual going-to-sleep position from non-left to left, if this was better for the baby.

Maternal age has been previously reported to affect sleep patterns in late pregnancy [18], although in this study, it was not significantly related to choice of left or non-left side going-to-sleep position in the last week. There was also no association between receiving advice on pregnancy sleep position from any source and sleep position, possibly due to inconsistency of the advice received. Furthermore, lack of association with gestation may have been because women in our study were in the third trimester with a median gestation of 35.7 weeks.

Strengths and limitations

This is the first survey in New Zealand to investigate maternal sleep knowledge, sleep position and influencing factors in late pregnancy. Responses were obtained from a representative sample [14] of multi-ethnic pregnant women in a community predominantly of low socioeconomic status. Although maternal sleep position was not able to be validated, participants were provided with a diagram of a bed to aid recall of their sleep position. A moderate correlation between women's recalled sleep time in the left side position and video evidence has recently been reported [18]. Information bias was reduced by participants and research assistants being unaware of the study objectives. In addition, there has been no formal public health recommendation on late pregnancy maternal sleep position in New Zealand.

Conclusions

Non-left, and in particular supine, sleep position in late pregnancy may be associated with an increased risk of stillbirth [1][2][3]. Promoting optimal going-to-sleep position in late pregnancy may therefore have the potential to reduce the incidence of late stillbirth. It was encouraging that most participants reported that their goingto-sleep position in the last week was side-lying. It was also positive that a large majority of women who usually went to sleep in a non-left position in late pregnancy reported that they would be able to change to a left side going-to-sleep position if that was recommended.

The finding that sleeping on the left-hand side of the bed is significantly associated with a left side going-tosleep position may assist women to more easily modify their sleep position. Furthermore, most women reported that they could change the side of the bed they slept on to achieve this. Our findings have the potential to assist with the development of a public health intervention on how to achieve optimal third trimester going-to-sleep position that can be applied in a multicultural setting.

:
Questionnaire. (DOCX 73 kb) Abbreviations aOR: Adjusted odds ratio; BMI: Body mass index; CI: Confidence interval

Table 1
1Self-reported maternal sleep in last weekResponse
n = 377 (%)

Table

Table 3
3Factors associated with non-left side sleep position (n = 375) OR Odds ratio, CI Confidence interval, BMI Body mass index *Statistically significant (p ≤ 0.05) Multivariable model is adjusted for all the variables in the table Maternal age, gestational age, and BMI were treated as continuous variables and ORs are for a 1 unit increaseVariable
Left side sleep
Non-left sleep
Univariable OR
Adjusted OR

(n = 114)
(n = 261)
(95% CI)
(95% CI)

n (row %)
n (row %)

Maternal age (years) [mean (SD)]
28.6 (5.7)
27.0 (5.4)
0.95 (0.91-0.99)*
0.97 (0.92-1.01)

Ethnicity (prioritised)

Maori
23 (26.4)
64 (73.6)
2.12 (1.11-4.05)*
2.64 (1.23-5.66)*

Pacific
43 (27.9)
111 (72.1)
1.96 (1.12-3.45)*
2.91 (1.46-5.78)*

Asian
13 (24.5)
40 (75.5)
2.34 (1.09-5.03)*
1.79 (0.79-4.05)

European & Other
35 (43.2)
46 (56.8)
Reference
Reference

Live with partner

No
19 (27.1)
51 (72.9)
Reference
Reference

Yes
95 (31.2)
210 (68.9)
0.82 (0.46-1.47)
1.36 (0.70-2.65)

Gestational age (weeks) [mean (SD)]
35.3 (3.6)
35.3 (3.4)
1.01 (0.94-1.07)
1.03 (0.96-1.10)

BMI [mean (SD)]
34.9 (7.6)
32.5 (7.1)
0.96 (0.93-0.99)*
0.93 (0.89-0.96)*

Sleeping on left side of bed

No
43 (20.0)
172 (80.0)
3.19 (2.02-5.04)*
3.29 (2.03-5.32)*

Yes
71 (44.4)
89 (55.6)
Reference
Reference

Received any advice on sleep position

No
36 (30.3)
83 (69.8)
1.01 (0.63-1.62)
0.99 (0.59-1.66)

Yes
78 (30.5)
178 (69.5)
Reference
Reference

AcknowledgementsWe thank the participants and their midwives, and Shireen Chua and the research assistants for support with recruitment and data collection.FundingCure Kids. Award number 5011. The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of this manuscript.Availability of data and materialsThe manuscript does not contain any individual person's identifiable data or information. The dataset analysed during the current study is available from the corresponding author on reasonable request.Authors' contributionsCompeting interestsAll authors declare that they have no competing interests.Consent for publication Not applicable.Ethics approval and consent to participate University of Auckland Human Participants Ethics Committee, Reference 011116 (February 2014). Ethics approval was given for participants to provide informed verbal consent at the time of recruitment, after receiving information about the study from research assistants, being provided with an information sheet and given the opportunity to ask questions. Voluntarily undertaking the anonymised self-complete survey on an electronic tablet signified implied consent.Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.• We accept pre-submission inquiries • Our selector tool helps you to find the most relevant journal Submit your next manuscript to BioMed Central and we will help you at every step:
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Unsolved Mystery Where Does Bluetongue Virus Sleep in the Winter?
1612 August 2008

Anthony Wilson
Karin Darpel
Philip Scott Mellor
Anthony Wilson
Karin Darpel
Philip Scott
Unsolved Mystery Where Does Bluetongue Virus Sleep in the Winter?

PLoS Biology | www.plosbiology.org PLoS Biology | www.plosbiology.org
61612 August 2008Abbreviations: BTV, bluetongue virus, WNV, West Nile virus Mellor are at the Institute for Animal Health, Pirbright Laboratory, Pirbright, Surrey, United Kingdom. * To whom correspondence should be addressed. Unsolved Mysteries discuss a topic of biological importance that is poorly understood and in need of research attention.
Citation: Wilson A, Darpel K, Mellor PS (2008) Where does bluetongue virus sleep in the winter? PLoS Biol 6(8): e210.

B luetongue virus (BTV) is spread by the bites of Culicoides midges (Figure 1), and can infect ruminant livestock such as cattle, sheep, and goats, wild ruminants such as deer, and camelids. Some infected animals develop the disease known as bluetongue, with clinical signs ranging from apathy and weight loss to swollen heads, tender feet and death (Figure 2). Historically a tropical and subtropical disease, bluetongue has become a regular visitor to southern Europe in the last decade [1,2]. Although growth in the global trade in livestock may have increased the frequency with which exotic viruses are introduced into Europe, the increasing tendency of those introduced strains to persist and spread is probably best explained by changes to the European climate [3], and several direct and indirect links between climate and BTV transmission have been identified [2]. BTV reached northern Europe for the first time in 2006, and affected around 2,000 holdings before reports ceased in early January 2007. The outbreak then re-emerged months later [4] and spread to a further 45,000 holdings by the end of the year, making it the most economically damaging outbreak of bluetongue ever seen [2,5].

Although this re-emergence was a timely reminder of the ability of BTV to escape detection for months at a time in temperate regions, the ability of BTV to "overwinter" has been recognised for decades (e.g., [6][7][8]). Both midge activity and virus replication in the midge cease at cool temperatures, interrupting transmission, but outbreaks sometimes resume after "silent" periods of several months-far longer than the typical lifespan of the adult vector or the normal period of infectious viraemia in a mammalian host [7][8][9]. Where, then, might the virus persist without detection during the winter months?

Where to Start? Lessons from Other Insect-Borne Diseases

The normal transmission cycle of a vector-borne disease such as bluetongue is shown in the left panel of Figure  3. Infectious vectors inject virus into hosts via saliva while feeding. Infected hosts then pass through a short incubation period before developing an infectious level of virus, and vectors that bite the host while virus levels are high may be infected. Ingested virus replicates in infected vectors until it reaches the salivary glands, at which point the vector becomes infectious and the cycle is completed. This same basic cycle of transmission is seen in vector-borne diseases from chikungunya to tick-borne encephalitis.

When contact between the primary vector population and primary host population is interrupted, there are three ways that a virus could theoretically persist: (1) in the vector population, (2) in the host population, or (3) via an alternative transmission cycle involving one or more novel vector or host populations. Persistence in the vector or host populations may be achieved via horizontal (direct) transmission between individuals, vertical transmission from infected parent to young, or persistence in individuals. Because insect vectors are generally infectious for life but relatively short-lived, persistence in individual vectors would require the survival of infected vectors for unusually long periods.

Examples of many of these potential routes have been seen in other vector-borne disease systems. Culex pipiens, an important vector of West Nile virus (WNV), survives the winter as overwintering adults that can tolerate temperatures as low as −25 °C (P. Reiter, personal communication), and that may be infected by WNV [10]. Vertical transmission in the vector population has been detected in several viruses, including Ross River virus [11] and WNV [12], and WNV may also be sexually transmitted between vectors [13]. Meanwhile, a number of arbovirus infections appear to be able to cross the mammalian placenta, including Getah virus, Ross River  [14,15], and birds that appear to have recovered from WNV may still harbour infectious virus in internal organs such as the spleen [13].

Overwintering in the Insect Vector

Because most species of Culicoides at northern latitudes survive the winter as larvae [16], it might appear that the most likely mechanism for overwintering is the vertical transmission of virus from infected vectors to offspring via the developing egg ("transovarial" transmission; see Figure 3). However, experiments designed to look for vertical transmission of BTV in Culicoides have consistently reported negative results (reviewed in [17]). One field study detected fragments of BTV RNA in larvae but no live virus [18], supporting the hypothesis that pores in the vitelline membrane sometimes permit proteins, RNA fragments, and other materials less than 11 nm in diameter to enter the developing egg, while mechanically preventing the passage of intact virus particles, which are much larger [19].

Might BTV be able to survive the winter in the adult vector population, then, as shown for West Nile virus? Although adult Culicoides are far less tolerant of sub-zero temperatures than Culex mosquitoes and are normally thought to survive no longer than 10-20 days [20], laboratory studies suggest that this lifespan may be extended by mild winter conditions, with individuals surviving for up to three months at 10 °C in the laboratory [21]. The winter of 2006-2007 was the mildest on record in Europe (J. Kennedy, personal communication), and small numbers of adult Culicoides vectors were caught throughout the winter period [22]. In mild winters such as this, it is possible that a small fraction of the infected adult Culicoides population might survive long enough to bridge the gap between transmission seasons (Figures 3 and 4). Adult Culicoides may also be sheltered from the worst conditions of winter to some degree by their choice of resting place. Although most north European Culicoides species were previously believed to be reluctant to enter buildings, studies during the current outbreak have suggested that small numbers may move indoors when outdoor temperatures begin to drop [23].

Overwintering in the Ruminant Population

BTV could also covertly persist in the ruminant population during the winter, whether by chronic or latent infection of some individuals, transmission across the placenta from mother to foetus, or horizontal transmission during sexual intercourse. Chronically infected hosts remain continually infectious for prolonged periods of time, while latent viruses such as herpes lie dormant within an infected host but can be stimulated to resume replication by certain events, such as when immunity is compromised due to stress or other infections or following the use of certain pharmaceuticals such as steroids. Because latent infections are characterised by the absence of detectable virus, this type of persistence causes the greatest headache for surveillance and control. However, since a chronic infection may involve only single organs, it is not as easily distinguishable from a truly latent infection as it might first appear; BTV and most other arboviruses are normally detected by testing blood samples, and virus infecting only certain organs of the body but absent from the bloodstream may escape detection.

There is some evidence to support the idea of chronic BTV infections in ruminants. Infectious BTV can be isolated from the blood of cattle for much longer than from sheep and goats, and although the vast majority of infections in cattle endure for less than 60 days, a fraction may last for much longer [24]. Such infections could permit the virus to persist for three to four months without infecting new hosts, and thereby survive short periods of vector absence ( Figures  3 and 4). Evidence for latent infection, meanwhile, was first reported over 30 years ago, when it was observed that feeding large numbers of uninfected vector Culicoides on apparently recovered cattle could stimulate the recrudescence of the virus [25]. Though this experiment was later criticised due to flaws in the research protocol, a more recent study confirmed that it was possible to isolate BTV from the skin of  apparently recovered sheep over two months post-infection following Culicoides feeding [26]. Although other studies have not yet replicated this result, it would provide an elegant and efficient mechanism for virus to reappear in exactly the correct place and time to re-infect the next vector generation.

In transplacental infections, virus infecting the mother crosses the chorion and invades the foetus. Since the gestation period of cattle is nine months (against five for sheep), the potential for the virus to bridge the seasonally vector-free period via this mechanism is clear (Figures 3 and  4). Transplacental transmission of BTV was first documented in the 1970s [27], and suggested that the outcome was very much dependent on the stage of pregnancy at which infection occurred. Infection in early pregnancy was likely to result in abortion or stillbirth, while foetuses infected at a late stage of pregnancy tended to clear the virus. Infection at an intermediate stage, before the foetus's immune system is fully developed, sometimes resulted in a prolonged infection, and some lambs infected in utero remained viraemic for up to two months after birth [27]. However, the virus strains used in these experiments had been passaged in artificial tissue culture systems, and the relevance of these findings to the transmission of field strains of BTV was questioned. Recent reports from northern Europe appear to indicate that the strain of BTV currently circulating has the potential to spread vertically in the ruminant population [28,29,30], although the fact that it has never been detected previously implies that only a subset of field strains may have this capacity.

Infected bulls and rams may also occasionally shed the virus in semen, possibly because of contaminating blood cells, and venereal transmission may thereby occur. However, all research suggests that this occurs only during the normal duration of viraemia, and current trade regulations require that breeding bulls and rams are tested for BTV before semen can be exported.

Other Possibilities

Various other overwintering mechanisms have been proposed, although generally with less supporting evidence than the mechanisms already described. For example, it has been suggested that BTV might be maintained in an as yet unknown reservoir host population with a long viraemia in which clinical signs either do not occur or go unnoticed. Such a reservoir host would need to demonstrate a duration of viraemia matching or exceeding that seen in cattle to account for most observed instances of overwintering, and although the duration of BTV viraemia in European wild ruminants has not been well studied, white-tailed deer and elk appear to show a detectable viraemia for only 16 days or less [31,32]. However, one study has suggested that viraemia in elk may resume up to three months postinfection in response to stress [31]. Coupled with the observation of relatively high levels of seroprevalence in red deer populations in Belgium during the current outbreak [33], this hypothesis may therefore warrant further investigation.  Other authors have suggested that, while BTV transmission is reduced by cold conditions, "overwintering" is effectively a consequence of intermittent surveillance, and that transmission within the recognised domestic ruminant hosts continues at low levels throughout the winter. Although most BTV cases are subclinical, and therefore a small number of infections might escape detection, this proposal has not received wide acceptance, and the occurrence of overwintering in regions such as northern Europe (where outdoor temperatures during the winter are indisputably below the requirements of the virus for replication in the vector) makes it even less likely. However, cold weather could, directly or indirectly, trigger behavioural changes in vector populations. Before malaria was eradicated from northern Europe, the winter stabling of livestock encouraged normally exophilic mosquito vectors to venture indoors, resulting in seasonal indoor malaria transmission [34]. Similarly, if adult Culicoides do enter buildings in the winter, they might experience conditions that are sufficiently warm for bloodfeeding all year round.

Vectors other than Culicoides could also have a role to play. Even in cold weather, the Culicoides lifespan is relatively short, but ticks may also occasionally act as biological vectors of BTV [35] and can live for several years. Furthermore, mechanical transmission of BTV has been shown in Melophagus ovinus, a wingless ectoparasitic fly that lives in the fleece of sheep [36], and may be possible by other species. Mechanical transmission is the physical transportation of infectious virus from one host to another, without extrinsic replication. Because extrinsic virus replication is not required for this type of transmission, the minimum temperature threshold for the completion of the transmission cycle is removed and transmission can occur at any time of year irrespective of climate.

Finally, oral transmission between mammalian hosts may also be a possibility. Cows will readily consume placental material following a birth, and although transmission between ruminants in this way has not been confirmed, at least one possible example has been reported [28]. Carnivores can also become infected after ingesting BTV-infected meat and organs [37]. BTV can also be spread mechanically between animals by humans, for example through contamination of vaccines [38], but this should not occur if high production and hygiene standards are adhered to.

Towards an Explanation

BTV is not limited to the core vector-borne disease transmission cycle commonly presented in textbooks. Multiple vectors and hosts may be involved, along with such diverse transmission routes as transplacental, mechanical, and oral routes. Rather than a single "missing link" enabling the virus to persist during the winter period, experiments have revealed a toolbox of possible mechanisms, with the potential to interact with and complement one another. For example, chronic infection of the uterus could increase the likelihood of transplacental transmission, which in turn may create chronically or latently infected calves. Examples of BTV overwintering in the literature can be found ranging from as little as three months to eight or nine. The shortest of these periods could be bridged by any of several candidate mechanisms, and the principal difficulty faced by the epidemiologist is narrowing down the list of suspects. At the other end of the scale, only a subset of these mechanisms or the interaction of two or more in sequence would be able to account for longer overwintering periods (Figure 4).

Although several of the mechanisms discussed in this paper were first suggested decades ago, interest in confirmatory and quantitative studies remained low for two reasons. Firstly, prior to the advent of molecular techniques, the subclinical nature of most BTV infections meant that it was both difficult and expensive to assert that transmission had stopped, and then to demonstrate that the re-emergence of bluetongue in a region was due to overwintering rather than reintroduction. Secondly, endemic regions such as South Africa or the United States have lived with bluetongue for so long that their agricultural sectors have adapted to its presence, avoiding the most susceptible breeds, vaccinating valuable animals, and accepting small losses rather than embarking upon expensive eradication programmes. Mechanisms that are important only for persistence therefore received little attention.

The recent spread of bluetongue into areas such as northern Europe, which are both highly susceptible to the economic effects of the disease and cold enough that classical transmission is interrupted for a significant part of the year, has stimulated field, laboratory, and analytical research into the mechanisms by which bluetongue may overwinter in temperate climes. The next steps for bluetongue research must be first, to establish these newly discovered transmission routes beyond reasonable doubt and second, to determine their importance for the transmission of BTV in the field. Some of this work has already begun: for example, several countries in northern Europe are conducting field studies to determine how readily their indigenous vector Culicoides enter animal housing [39], and the Institute for Animal Health, the Veterinary Laboratories Agency, and Animal Health are currently collaborating on a project to determine the degree to which transplacental transmission of BTV   be occurring in the current outbreak. Previous studies of similar diseases may also suggest productive approaches. For instance, direct surveillance for inactive adult vectors during the winter confirmed that they represented a potential mechanism for the overwintering of WNV [10], and similar surveillance of Culicoides populations, possibly via suction sampling, might shed further light on the potential for this route to maintain BTV during the winter months. Such detective work is not purely of interest for understanding the current outbreak in northern Europe. Confirmation of transplacental transmission of BTV in the field, for example, would have drastic consequences for international trade.

However, the epidemiology of bluetongue and other vector-borne diseases is determined by a number of factors, ranging from molecular variation in virus strains, through regional farm management and animal husbandry approaches, to spatial and temporal patterns of change in land use or climate detectable only via detailed analysis of high-resolution climate data or remotely sensed imagery. To achieve a full understanding of the epidemiology of diseases such as bluetongue will therefore require not only short-term independent entomological or veterinary studies but a commitment to truly interdisciplinary programmes of study over longer periods, incorporating approaches ranging in scale from molecular biology and virology through entomology and veterinary science to land use and climate modelling. Perhaps most importantly, the fact that we are now having to re-examine so many basic questions about the behaviour of Culicoides illustrates that we neglect basic studies of the ecology of insect species capable of acting as vectors of disease at our peril.

The existence of so many potential overwintering mechanisms for viruses such as BTV and WNV may also teach us more general lessons about the capacity for other medically or epidemiologically important vector-borne diseases to survive in temperate zones with seasonal vector absence. In particular, the risk to northern Europe from the BTV-related epizootic haemorrhagic disease virus (which also affects ruminants) and African horse sickness virus (which affects equids) should be re-evaluated. Consideration of the routes reviewed here may also be useful when assessing the risk of re-emergence of outbreaks of insect-borne viruses not previously seen in Europe, such as the 2007 outbreak of chikungunya virus in Italy. Meanwhile, as long as our understanding of overwintering in the field remains poor, the reappearance of BTV in northern Europe this year seems both inevitable and imminent.

Figure 1 .
1Blood-Feeding Culicoides Midges virus, and Western equine encephalitis

doi:10.1371/journal.pbio.0060210.g002

Figure 2 .
2Moderate (Left) and Severe (Right) Clinical Signs of Bluetongue in Sheep

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Figure 3 .
3The Transmission of Bluetongue Virus in Summer (Left) and Winter (Right) Mechanical transmission, sexual transmission, and alternative vector and host species not shown.

doi:10.1371/journal.pbio.0060210.g004

Figure 4 .
4The Ability of Various Mechanisms to Explain Observed Instances of Overwintering
PLoS Biology | www.plosbiology.org
August 2008 | Volume 6 | Issue 8 | e210
AcknowledgmentsThe authors would like to thank Simon Gubbins, Simon Carpenter, and Peter Mertens of the Institute for Animal Health and Paul Reiter of the Institut Pasteur for helpful discussions of the issues in this article, and John Kennedy of the Met Office Hadley Centre for providing information on seasonal European temperature anomalies.Funding. This work was funded by the Biotechnology and Biological Sciences Research Council (grant numbers BBS/B/00603, BB/G529075/1, strategic core grant 1146) and the UK Department for Environment, Food and Rural Affairs (grant number SE4104).
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