Stillbirths: rates, risk factors and potential for ...



LANCET ENDING PREVENTABLE STILLBIRTHS SERIES Paper 2Stillbirths: rates, risk factors and potential for progress towards 2030AuthorsJoy E Lawn, Hannah Blencowe, Peter Waiswa, Agbessi Amouzou, Colin Mathers, Dan Hogan, Vicki Flenady, J Frederik Fr?en , Zeshan U Qureshi, Claire Calderwood, Suhail Shiekh, Fiorella Bianchi Jassir, Danzhen You, Elizabeth M. McClure, Matthews Mathai, Simon CousensFor The Lancet Ending Preventable Stillbirths Series study group (J Frederik Fr?en, Joy E Lawn, Alexander Heazell, Vicki J Flenady, Mary Kinney, Luc de Bernis, Hannah Blencowe, Susannah Hopkins Leisher)With The Lancet Stillbirth Epidemiology Investigator group (see end of paper for list of members)AffiliationsMaternal Reproductive & Child Health (MARCH) Centre, London School of Hygiene & Tropical Medicine (Professor Joy E Lawn, FRCPCH; Hannah Blencowe, MRCPCH; Professor Simon Cousens, DipMathstat, Suhail Shiekh MSc, Fiorella Bianchi Jassir MSc), and Saving Newborn Lives/Save the Children USA (JEL and HB), MN Centre of Excellence, Makerere University and INDEPTH Maternal Newborn Working Group, School of Public Health, Uganda (Peter Waiswa PhD), UNICEF, New York, USA (Agbessi Amouzou PhD and Danzhen Yu PhD), World Health Organization, Geneva, Switzerland (Colin Mathers PhD, Dan Hogan PhD, Matthews Mathai PhD), Mater Hospital, Brisbane, Australia (Vicki Flenady, PhD); Department of International Public Health, Norwegian Institute of Public Health, Oslo, Norway (Professor J F Fr?en, PhD), University College London (Zeshan Qureshi, BM), Queen Mary University of London (Claire Calderwood, BM), Research Triangle Institute, Durham, NC, USA (E McClure, PhD).Corresponding authorProfessor JE Lawn, Maternal Reproductive & Child Health (MARCH) Centre, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT joy.lawn@lshtm.ac.uk Words4777Figures 3Tables 3Panels2Webappendix 35 pages more of details, plus 114 references to reduce manuscriptAbstractThere were an estimated 2.7 million third trimester stillbirths in 2015 (uncertainty range: 2.5 – 3.0 million). Stillbirths have reduced more slowly than maternal or child mortality, which were explicitly targeted in the Millennium Development Goals.? The Every Newborn Action Plan targets ≤12 stillbirths per 1000 births in every country by 2030. Ninety-two mainly high-income countries have already met this target, although with marked disparities. At least 67 countries, particularly in Africa and conflict affected areas will have to double current progress. Most (98%) stillbirths are in low and middle-income countries. Improved care at birth is essential to prevent 1.3 million intrapartum stillbirths, end preventable maternal and neonatal deaths, and also improve child development.?Estimates for stillbirth causation are impeded by multiple classification systems, but for 18 countries with reliable data, congenital abnormalities account for a median of only 7.4%. Many conditions associated with stillbirths are potentially modifiable, and often co-exist such as maternal infections (population attributable fraction (PAF): malaria 8.2%, syphilis 7.7%), non-communicable diseases, nutrition and lifestyle factors (PAF around 10%) and age>35yrs (PAF: 6.7%). Common causal pathways are through impaired placental function, either leading to fetal growth restriction and/or preterm labour, or secondary to prolonged pregnancy (PAF: 14.2%). Two-thirds of newborns have their birth registered. However, less than 5% of neonatal deaths have death registration, and even fewer stillbirths. Recording and registering all facility births, stillbirths, neonatal, and maternal deaths would substantially increase data availability. Improved data alone will not save lives, but provide a tool for targeting interventions to reach >7500 women every day all over the world who experience the reality of stillbirth.Words 266 Key messagesWhat is happening to stillbirth rates? At the end of the Millennium Development Goal (MDG) era there are 2.7 million (uncertainty range: 2.5 – 3.0 million) third trimester stillbirths annually. Stillbirth rates have declined more slowly since 2000 (Average Annual Rate of Reduction (ARR), 1.8%), than either maternal (ARR=3.4%) or post-neonatal child mortality (ARR=4.5%) which had MDG targets and consequently received more global and country level attention. Better data are essential to accelerate progress towards the target of ≤12 stillbirths per 1000 births in every country by 2030 as outlined in the Every Newborn Action Plan (ENAP), linked to United Nations Secretary General’s Every Woman Every Child. Where to focus? 10 countries account for two-thirds of stillbirths and most neonatal (60%) and maternal (58%) deaths estimated in 2015. Sixty-seven countries need to at least double current progress in reducing stillbirths, many of these in Africa. The highest stillbirth rates (SBR) are in conflict and emergency areas. Over 60% of stillbirths are in rural areas, affecting the poorest families. However, even in the 92 countries with a SBR less than 12 per 1000 marked disparities remain between and within countries. When and where in the health system to focus? Each year there are an estimated 1.3 million intrapartum stillbirths (deaths during labour), despite two-thirds of births worldwide now being in health facilities. High coverage of good quality care during labour and birth is key, and would also reduce maternal and neonatal deaths, prevent disability and improve child development, giving a high return on investment. Improved quality antenatal care is also important to maximise maternal and fetal well-being, to detect and manage underlying conditions, and to promote healthy behaviours and birth planning.Which conditions to focus on? There is a myth that most stillbirths are inevitable due to non-preventable congenital abnormalities, yet for countries with reliable data congenital abnormalities account for a median of only 7.4% of stillbirths. Conditions where population attributable fraction (PAF) could be estimated at global level include: maternal age>35yrs (PAF 6.7%), maternal infections (PAF malaria 8.2%, syphilis 7.7%), non-communicable diseases, nutrition and lifestyle factors, many of which co-exist (PAF each around 10%) and prolonged pregnancy (PAF 14.2%). Stillbirths commonly occur via fetal growth restriction and/or preterm labour. Which data are required for action? Two-thirds of the world’s newborns have birth certificate, but death registration coverage is even lower at <5% of neonatal deaths and even fewer stillbirths. Recording and registering all facility births, stillbirths, neonatal deaths, and maternal deaths would substantially increase data availability. Reliable measurement of stillbirths outside facilities using household surveys remains problematic, yet no research is addressing this issue. Little has been invested in improving coverage data for maternal and newborn health interventions including those specific to stillbirths. The ENAP measurement improvement roadmap, includes coverage indicator validation, and development of tools such as a minimum perinatal dataset and perinatal audit, offering opportunities to improve data availability and use. IntroductionThe Millennium Development Goals (MDGs) demonstrated the value of health outcome targets to drive change. Maternal (MDG5) and under-five mortality (MDG4) have been halved, with progress still accelerating, most notably for child mortality, with the annual rate of reduction (ARR) improving from 1.2% (1990-1995) to 4% (2005-2013). ADDIN EN.CITE <EndNote><Cite><Author>UN Inter-agency Group for Child Mortality Estimation (UN-IGME)</Author><Year>2014</Year><RecNum>176</RecNum><DisplayText><style face="superscript">1</style></DisplayText><record><rec-number>176</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1435047267">176</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>UN Inter-agency Group for Child Mortality Estimation (UN-IGME),</author></authors></contributors><titles><title>Levels and Trends in Child Mortality</title><secondary-title> The world’s 2.7 million neonatal deaths (first 28 days after birth) have increased prominence on national and global agendas, primarily since they account for 45% of under-five deaths globally. ADDIN EN.CITE <EndNote><Cite><Author>UN Inter-agency Group for Child Mortality Estimation (UN-IGME)</Author><Year>2014</Year><RecNum>176</RecNum><DisplayText><style face="superscript">1</style></DisplayText><record><rec-number>176</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1435047267">176</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>UN Inter-agency Group for Child Mortality Estimation (UN-IGME),</author></authors></contributors><titles><title>Levels and Trends in Child Mortality</title><secondary-title> Attention was not driven by numbers regarding millions of newborn deaths, but more by recognition that neonatal mortality reduction was essential for the MDG4 child mortality target, accounting for almost half of child deaths.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EYXJtc3RhZHQ8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy

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ADDIN EN.CITE.DATA 2,3 In contrast, stillbirths (see panel 1 for definitions) were not included in the MDGs and are not tracked by either the United Nations or the Global Burden of Disease, ADDIN EN.CITE <EndNote><Cite><Author>Lawn</Author><Year>2011</Year><RecNum>74</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>74</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434442859">74</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lawn, J. E.</author><author>Blencowe, H.</author><author>Pattinson, R.</author><author>Cousens, S.</author><author>Kumar, R.</author><author>Ibiebele, I.</author><author>Gardosi, J.</author><author>Day, L. T.</author><author>Stanton, C.</author></authors></contributors><auth-address>Saving Newborn Lives/Save the Children, Cape Town, South Africa. joylawn@yahoo.co.uk</auth-address><titles><title>Stillbirths: Where? When? Why? How to make the data count?</title><secondary-title>Lancet</secondary-title></titles><periodical><full-title>Lancet</full-title></periodical><pages>1448-63</pages><volume>377</volume><number>9775</number><edition>2011/04/19</edition><keywords><keyword>Cause of Death</keyword><keyword>Data Collection</keyword><keyword>Developed Countries/statistics &amp; numerical data</keyword><keyword>Developing Countries/statistics &amp; numerical data</keyword><keyword>Epidemiologic Measurements</keyword><keyword>Female</keyword><keyword>Fetal Death/classification</keyword><keyword>Humans</keyword><keyword>Maternal Mortality</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy Complications</keyword><keyword>Stillbirth/ epidemiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 23</date></pub-dates></dates><isbn>1474-547X (Electronic)&#xD;0140-6736 (Linking)</isbn><accession-num>21496911</accession-num><urls><related-urls><url>(10)62187-3/abstract</url></related-urls></urls><electronic-resource-num>10.1016/s0140-6736(10)62187-3</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>4 both of which count burden only after a live birth.PEVuZE5vdGU+PENpdGUgRXhjbHVkZUF1dGg9IjEiPjxZZWFyPjIwMTU8L1llYXI+PFJlY051bT4y

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ADDIN EN.CITE.DATA 1,5 Despite previous estimates showing large numbers of stillbirths (2.6 million in 2009), ADDIN EN.CITE <EndNote><Cite><Author>Cousens</Author><Year>2011</Year><RecNum>71</RecNum><DisplayText><style face="superscript">6</style></DisplayText><record><rec-number>71</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434442859">71</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cousens, S.</author><author>Blencowe, H.</author><author>Stanton, C.</author><author>Chou, D.</author><author>Ahmed, S.</author><author>Steinhardt, L.</author><author>Creanga, A. A.</author><author>Tuncalp, O.</author><author>Balsara, Z. P.</author><author>Gupta, S.</author><author>Say, L.</author><author>Lawn, J. E.</author></authors></contributors><auth-address>London School of Hygiene and Tropical Medicine, London, UK. simon.cousens@lshtm.ac.uk</auth-address><titles><title>National, regional, and worldwide estimates of stillbirth rates in 2009 with trends since 1995: a systematic analysis</title><secondary-title>Lancet</secondary-title></titles><periodical><full-title>Lancet</full-title></periodical><pages>1319-30</pages><volume>377</volume><number>9774</number><edition>2011/04/19</edition><keywords><keyword>Female</keyword><keyword>Global Health</keyword><keyword>Humans</keyword><keyword>Models, Statistical</keyword><keyword>Pregnancy</keyword><keyword>Stillbirth/ epidemiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 16</date></pub-dates></dates><isbn>1474-547X (Electronic)&#xD;0140-6736 (Linking)</isbn><accession-num>21496917</accession-num><urls><related-urls><url>(10)62310-0/abstract</url></related-urls></urls><electronic-resource-num>10.1016/s0140-6736(10)62310-0</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>6 global attention remains low. Analyses of development aid reveal how rarely stillbirths were mentioned by donors - only 4 times in more than 2 million disbursements totalling $1,599 billion (constant 2013 USD) from 2002-13. ADDIN EN.CITE <EndNote><Cite><Author>Froen</Author><Year>2015</Year><RecNum>147</RecNum><DisplayText><style face="superscript">7,8</style></DisplayText><record><rec-number>147</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434444836">147</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Froen, J. F.</author></authors></contributors><titles><title>Stillbirths: Progress and Unfinished Business</title><secondary-title>Lancet - in press</secondary-title></titles><periodical><full-title>Lancet - in press</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite><Cite><Author>Arregoces L</Author><Year>2015</Year><RecNum>148</RecNum><record><rec-number>148</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434444967">148</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Arregoces L, </author><author>Daly F, </author><author>Pitt C, </author><author>Hsu J, </author><author>Martinez-Alvarez M, </author><author>Greco G, </author><author>Mills A, </author><author>Berman P, </author><author>Borghi J </author></authors></contributors><titles><title>Countdown to 2015: changes in official development assistance to reproductive, maternal, newborn and child health, and assessment of progress between 2003 and 2012. </title><secondary-title>Lancet Glob Health</secondary-title></titles><periodical><full-title>Lancet Glob Health</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>7,8 The mortality focus during the MDG-era has also catalysed investments in data improvement. For example, child mortality data have increased through nationally representative surveys, the largest source for child mortality data in low and lower-middle income countries (). Many middle income countries have strengthened child death reporting in routine systems including vital registration. The frequency and visibility of maternal, child and neonatal mortality estimates have increased, with inclusion of neonatal mortality to annual UNICEF reports since 2009. ADDIN EN.CITE <EndNote><Cite><Author>UNICEF</Author><RecNum>263</RecNum><DisplayText><style face="superscript">9</style></DisplayText><record><rec-number>263</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1435563980">263</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>UNICEF,</author><author>USAID,</author><author>The World Health Organization,</author></authors></contributors><titles><title>A promise renewed - ending preventable child and maternal deaths</title><secondary-title> In contrast stillbirth rate (SBR) data, although available in over 100 countries through civil registration and vital statistics systems (CRVS) or registry data, have not been routinely collated. Nor has there been investment in improving stillbirth data through household surveys, which remain the main SBR data source for most high burden countries. To date, only one set of national SBR estimates has been undertaken with World Health Organization (WHO). ADDIN EN.CITE <EndNote><Cite><Author>Cousens</Author><Year>2011</Year><RecNum>71</RecNum><DisplayText><style face="superscript">6</style></DisplayText><record><rec-number>71</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434442859">71</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cousens, S.</author><author>Blencowe, H.</author><author>Stanton, C.</author><author>Chou, D.</author><author>Ahmed, S.</author><author>Steinhardt, L.</author><author>Creanga, A. A.</author><author>Tuncalp, O.</author><author>Balsara, Z. P.</author><author>Gupta, S.</author><author>Say, L.</author><author>Lawn, J. E.</author></authors></contributors><auth-address>London School of Hygiene and Tropical Medicine, London, UK. simon.cousens@lshtm.ac.uk</auth-address><titles><title>National, regional, and worldwide estimates of stillbirth rates in 2009 with trends since 1995: a systematic analysis</title><secondary-title>Lancet</secondary-title></titles><periodical><full-title>Lancet</full-title></periodical><pages>1319-30</pages><volume>377</volume><number>9774</number><edition>2011/04/19</edition><keywords><keyword>Female</keyword><keyword>Global Health</keyword><keyword>Humans</keyword><keyword>Models, Statistical</keyword><keyword>Pregnancy</keyword><keyword>Stillbirth/ epidemiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 16</date></pub-dates></dates><isbn>1474-547X (Electronic)&#xD;0140-6736 (Linking)</isbn><accession-num>21496917</accession-num><urls><related-urls><url>(10)62310-0/abstract</url></related-urls></urls><electronic-resource-num>10.1016/s0140-6736(10)62310-0</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>6 Hence, stillbirths were without a high profile target or accountability loop, as highlighted in several MDG reports.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Db3VudGRvd24gdG8gMjAxNTwvQXV0aG9yPjxZZWFyPjIw

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ADDIN EN.CITE.DATA 10-12The Every Newborn Action Plan (ENAP) launched in mid-2014 with a World Health Assembly resolution, endorsed by all countries and supported by over 80 partners, ADDIN EN.CITE <EndNote><Cite><Author>UNICEF</Author><Year>2013</Year><RecNum>264</RecNum><DisplayText><style face="superscript">13</style></DisplayText><record><rec-number>264</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1435567244">264</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>UNICEF,</author><author>The World Health Organization,</author></authors></contributors><titles><title>Every Newborn: An action plan to end preventable newborn deaths </title></titles><dates><year>2013</year></dates><urls></urls></record></Cite></EndNote>13 supports the UN Secretary General’s global initiative Every Woman Every Child, linking with “Ending Preventable Maternal Mortality” and “A Promise Renewed” for children. During consultations for ENAP development country representatives repeatedly stated that a target for stillbirths was needed to ensure accountability.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYXduPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA 3,13 ObjectivesThis paper reviews the status of stillbirth around the world and progress since the 2011 Lancet Stillbirth Series. We summarise the following new analyses, with the aim of informing action to meet 2030 stillbirth targets: Progress and projections for stillbirth rates (SBRs), in 195 countries, with new estimates and trends from 2000-2015, plus analyses to examine national SBR reductions required to reach the ENAP target of 12 or fewer stillbirths per 1000 total births in all countries by 2030.Priorities to accelerate progress towards preventing stillbirths, notably where and when to focus, including the first published global comparative risk factor analysis of potentially modifiable demographic, infectious, non-communicable disease (NCD) and lifestyle factors associated with stillbirth.3 Improvements in national stillbirth data since the Lancet Stillbirth 2011 series and gaps remaining. Methods DefinitionsThere is now wider recognition and use of the International Classification of Disease (ICD) and WHO recommendations for international stillbirth rate reporting (panel 1), ADDIN EN.CITE <EndNote><Cite><Author>World Health Organization</Author><Year>2010</Year><RecNum>177</RecNum><DisplayText><style face="superscript">14</style></DisplayText><record><rec-number>177</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1435047923">177</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>World Health Organization,</author></authors></contributors><titles><title>International Classification of Diseases 10th revision (ICD-10)</title><secondary-title> facilitating comparisons, whilst recognising that countries may apply other definitions for internal use. Definition variability occurs mainly amongst high income countries (HIC) with a range from 20 weeks gestational age (GA) upwards, with many countries lowering the gestational age for reporting due to increasing survival at earlier gestational ages with neonatal intensive care.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GbGVuYWR5PC9BdXRob3I+PFllYXI+MjAxNTwvWWVhcj48

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ADDIN EN.CITE.DATA 4,15However, as more countries report stillbirth data, issues with respect to the ICD classification are now clearer. ICD was developed before GA reporting became standard and prioritises birthweight over GA, and incorrectly assumes equivalence between birth weight and GA (panel 1). ADDIN EN.CITE <EndNote><Cite><Author>Blencowe</Author><Year>2015</Year><RecNum>137</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>137</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1439912058">137</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Blencowe, H,</author><author>Cousens S, </author><author>Bianchi Jassir F, </author><author>Say L, </author><author>Chou D, </author><author>Mathers C, </author><author>Hogan D, </author><author>Shiekh S, </author><author>Qureshi ZU, </author><author>You D, </author><author>Lawn JE,</author><author>For the Lancet Stillbirth investigator group.</author></authors></contributors><titles><title>National, regional and worldwide estimates of stillbirth rates in 2015, with trends from 2000</title><secondary-title>submitted to Lancet Global Health</secondary-title></titles><periodical><full-title>submitted to Lancet Global Health</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>16 GA-based cut off is more appropriate, as a better predictor of maturity and hence viability, than birthweight.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Nb2hhbmdvbzwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+

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ADDIN EN.CITE.DATA 17 We propose that for international comparison the definition focus on a GA threshold for stillbirths, rather than birthweight, and be included in ICD 11. In this Lancet series we use the ≥28 weeks definition for stillbirth epidemiological estimates. ADDIN EN.CITE <EndNote><Cite><Author>Blencowe</Author><Year>2015</Year><RecNum>137</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>137</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1439912058">137</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Blencowe, H,</author><author>Cousens S, </author><author>Bianchi Jassir F, </author><author>Say L, </author><author>Chou D, </author><author>Mathers C, </author><author>Hogan D, </author><author>Shiekh S, </author><author>Qureshi ZU, </author><author>You D, </author><author>Lawn JE,</author><author>For the Lancet Stillbirth investigator group.</author></authors></contributors><titles><title>National, regional and worldwide estimates of stillbirth rates in 2015, with trends from 2000</title><secondary-title>submitted to Lancet Global Health</secondary-title></titles><periodical><full-title>submitted to Lancet Global Health</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>16 An intrapartum stillbirth (IPSB) is a stillbirth occurring after the onset of labour, but before birth. Fresh stillbirth is commonly used as surrogate marker (panel 1).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYXduPC9BdXRob3I+PFllYXI+MjAwNTwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA 18 Antepartum stillbirths (APSB) occur prior to the onset of labour.Data inputs and analysesPanel 2 and the webappendix summarise the data inputs and analyses. SBR data were available from 157 of 195 countries, with high quality CRVS data from 54 countries. SBR estimates were developed with WHO including country consultation and presented at UN Inter-agency Group for Mortality Estimation (UN-IGME). ADDIN EN.CITE <EndNote><Cite><Author>Blencowe</Author><Year>2015</Year><RecNum>137</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>137</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1439912058">137</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Blencowe, H,</author><author>Cousens S, </author><author>Bianchi Jassir F, </author><author>Say L, </author><author>Chou D, </author><author>Mathers C, </author><author>Hogan D, </author><author>Shiekh S, </author><author>Qureshi ZU, </author><author>You D, </author><author>Lawn JE,</author><author>For the Lancet Stillbirth investigator group.</author></authors></contributors><titles><title>National, regional and worldwide estimates of stillbirth rates in 2015, with trends from 2000</title><secondary-title>submitted to Lancet Global Health</secondary-title></titles><periodical><full-title>submitted to Lancet Global Health</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>16Data on timing of stillbirths (antepartum or intrapartum) are still lacking for the majority of countries, with 130 having no useable data (Panel 2, webappendix). Although Intrapartum Stillbirth rate (IPSBR) data should be available from most facility birth registers, these data are infrequently collated at a national level, even in HIC. The analyses of causes, notably congenital abnormalities, and risk factors are summarised in Panel 2, and the webappendix.Results and DiscussionProgress in reducing stillbirths and meeting 2030 targetsIn 2015, an estimated 2.7 million babies (uncertainty range:2.5 – 3.0 million) will die before birth during the last trimester of pregnancy, a worldwide rate of 18.9 stillbirths per 1000 total births (uncertainty range:17.4 – 21.1). ADDIN EN.CITE <EndNote><Cite><Author>Blencowe</Author><Year>2015</Year><RecNum>137</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>137</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1439912058">137</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Blencowe, H,</author><author>Cousens S, </author><author>Bianchi Jassir F, </author><author>Say L, </author><author>Chou D, </author><author>Mathers C, </author><author>Hogan D, </author><author>Shiekh S, </author><author>Qureshi ZU, </author><author>You D, </author><author>Lawn JE,</author><author>For the Lancet Stillbirth investigator group.</author></authors></contributors><titles><title>National, regional and worldwide estimates of stillbirth rates in 2015, with trends from 2000</title><secondary-title>submitted to Lancet Global Health</secondary-title></titles><periodical><full-title>submitted to Lancet Global Health</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>16 In 2000 the estimated SBR was 24.9, implying an ARR of 1.8% between 2000 and 2015. Thus, while some progress has been made, it has been slower than for maternal (ARR 3.4%), neonatal (ARR 3.1%) and post-neonatal under-5 child mortality (ARR 4.5%) over the same period. For every country to reach the ENAP stillbirth target of 12 or less by 2030 ADDIN EN.CITE <EndNote><Cite><Author>UNICEF</Author><Year>2013</Year><RecNum>264</RecNum><DisplayText><style face="superscript">13</style></DisplayText><record><rec-number>264</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1435567244">264</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>UNICEF,</author><author>The World Health Organization,</author></authors></contributors><titles><title>Every Newborn: An action plan to end preventable newborn deaths </title></titles><dates><year>2013</year></dates><urls></urls></record></Cite></EndNote>13 (Figure 1A), a global average ARR of 4.3% will be required from 2015, more than double the current ARR. Yet this global average hides regional variation. Despite slow progress overall, in every region some countries are reducing stillbirths faster than their neighbours (Figure 1B). In Bangladesh, where the SBR ARR is 2.8%, the total fertility rate (TFR) has halved since 2000, and coverage of key maternal-newborn interventions has increased including four antenatal care (ANC) visits (ANC4) (Average Annual Rate of Change (ARC)=6.5% (regional median=3.1%)) and birth with a skilled attendant (ARC=7.1% (regional median=2.9%). PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FbCBBcmlmZWVuPC9BdXRob3I+PFllYXI+MjAxNDwvWWVh

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ADDIN EN.CITE.DATA 20 Even in HIC, such as Netherlands, progress is possible, with improvements in ANC and care at birth, wide-scale perinatal audit, coupled with a focus on women’s health before and during pregnancy. ADDIN EN.CITE <EndNote><Cite><Author>Flenady</Author><Year>2015</Year><RecNum>150</RecNum><DisplayText><style face="superscript">15</style></DisplayText><record><rec-number>150</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434445384">150</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Flenady, V.</author></authors></contributors><titles><title>Stillbirth: A renewed case for action in high-income countries</title><secondary-title>Lancet in press</secondary-title></titles><periodical><full-title>Lancet in press</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>15Priorities for action to accelerate progress to prevent stillbirthsWhere geographically to focus to close the gap? For many countries, achieving the SBR target by 2030 will require concerted efforts. At least 67 countries will need to more than double their current annual stillbirth ARR. The African region has the highest SBRs and the slowest rates of progress, especially countries with conflicts and emergencies (Figure 1B) (webappendix). Thus, at current rates of progress it will be over 160 years before the average pregnant woman in Africa has the same chance of her baby being born alive as does a woman in a HIC today (Figure 1C), and even longer for women in the countries making the slowest progress. While the Sustainable Development Goals (SDGs) aim for convergence within a generation, with women and babies in all countries having the same chance of survival, equity gaps between regions and countries will widen over time, unless current SBR trends change. This is true even for HICs which have an average SBR of 3.3 per 1000 total births, but with substantial variation between countries, from 1.4 (Finland) to 9.4 (Ukraine) (Figure 1B). Almost all stillbirths occur in Low and Middle Income Countries (LMICs) (98%) with three-quarters in sub-Saharan Africa (SSA) and South Asia (Figure 2). The 10 countries with the most stillbirths account for 53% of all livebirths, 65% of all stillbirths and most maternal (58%) and neonatal (62%) deaths (Table 1). Population size is an important determining factor, but the rankings shift with changes in mortality risk and fertility. For example Brazil graduated from the ten countries with highest neonatal deaths and stillbirths through dramatic falls in both fertility and stillbirth risk. In contrast several African countries with continuing high fertility and SBRs are now among the ten countries with the most stillbirths, notably Tanzania and Uganda. Tanzania met MDG4 for child survival but reductions in maternal and neonatal mortality and especially stillbirths have been slower.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BZm5hbi1Ib2xtZXM8L0F1dGhvcj48WWVhcj4yMDE1PC9Z

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ADDIN EN.CITE.DATA 21 Challenging the myth that SBR or MNR reduction results in population growth, in many countries the reductions in NMR and SBR coincided with transition to low fertility, including Peru and Bangladesh (webappendix). ADDIN EN.CITE <EndNote><Cite><Author>Lithell</Author><Year>1992</Year><RecNum>268</RecNum><DisplayText><style face="superscript">22</style></DisplayText><record><rec-number>268</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1435614645">268</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lithell, U. B.</author><author>Rosling, H.</author><author>Hofvander, Y.</author></authors></contributors><titles><title>Children&apos;s deaths and population growth</title><secondary-title>Lancet</secondary-title></titles><periodical><full-title>Lancet</full-title></periodical><pages>377-8</pages><volume>339</volume><number>8789</number><edition>1992/02/08</edition><keywords><keyword>Birth Rate</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Humans</keyword><keyword>Mortality</keyword><keyword>Nigeria</keyword><keyword>Population Growth</keyword><keyword>Sweden</keyword></keywords><dates><year>1992</year><pub-dates><date>Feb 8</date></pub-dates></dates><isbn>0140-6736 (Print)&#xD;0140-6736 (Linking)</isbn><accession-num>1346463</accession-num><urls><related-urls><url>(92)91704-C/abstract</url></related-urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>22When to focus? Worldwide in 2015 around half of stillbirths, more than 1.3 million (range: 1.2 – 1.6 million), occurred during labour (Figure 2). The proportion of stillbirths that are intrapartum varies from 10.0% (range:5.5-18.4%) in Developed region to 59.3% (range: 32.0-84.0%) in South Asia (webappendix). The majority of intrapartum stillbirths occur in countries with low coverage of timely, high-quality care around the time of birth. More than 40 million women give birth unattended at home each year. Improving access to high quality intrapartum care is essential for reducing preventable stillbirths, with the added benefits of reducing the 46% of maternal deaths during labour, one million neonatal deaths occurring on their birthday, reducing long-term disability, and enhancing child development.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYXduPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA 3 Where in the health system? Given two-thirds of births worldwide occur in health facilities, most stillbirths are delivered in facilities. Hence high quality facility care, along with investments including community demand and birth planning, should be the first focus for stillbirth prevention. Despite increasing urbanisation, with the majority of the world now residing in cities, in South Asia and especially in Africa, around two-thirds of stillbirths are still rural. Rural families are often the poorest, with limited access to midwifery care, family planning services, and emergency obstetric care, including Caesarean section, resulting in high birth rates, and high stillbirth risk.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FbCBBcmlmZWVuPC9BdXRob3I+PFllYXI+MjAxNDwvWWVh

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ADDIN EN.CITE.DATA 19 Even in high income countries, SBR may be higher for rural areas. ADDIN EN.CITE <EndNote><Cite><Author>Ibiebele</Author><Year>2014</Year><RecNum>371</RecNum><DisplayText><style face="superscript">23</style></DisplayText><record><rec-number>371</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1439964265">371</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ibiebele, I.</author><author>Coory, M.</author><author>Boyle, F.</author><author>Humphrey, M.</author><author>Vlack, S.</author><author>Flenady, V.</author></authors></contributors><auth-address>Translating Research Into Practice (TRIP) Centre, Mater Research Institute-University of Queensland, Brisbane, Qld, Australia; School of Population Health, University of Queensland, Brisbane, Qld, Australia.</auth-address><titles><title>Stillbirth rates among indigenous and non-indigenous women in Queensland, Australia: is the gap closing?</title><secondary-title>BJOG</secondary-title></titles><periodical><full-title>BJOG</full-title></periodical><edition>2014/09/04</edition><keywords><keyword>Aboriginal and Torres Strait Islander</keyword><keyword>cause of death</keyword><keyword>fetal death</keyword><keyword>indigenous</keyword><keyword>stillbirth</keyword><keyword>trends</keyword><keyword>urban</keyword></keywords><dates><year>2014</year><pub-dates><date>Sep 3</date></pub-dates></dates><isbn>1471-0528 (Electronic)&#xD;1470-0328 (Linking)</isbn><accession-num>25183370</accession-num><urls><related-urls><url> Even short delays in accessing appropriate care can result in death or disability for newborns and women.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5VcGFkaHlheTwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+

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ADDIN EN.CITE.DATA 27,28 National SBRs show a strong ecological association with coverage of care (webappendix). Higher national coverage of ANC is strongly associated with lower antepartum SBRs. While WHO recommends a four-visit ANC model for low-risk populations, these policies are currently being reviewed. ADDIN EN.CITE <EndNote><Cite><Author>The World Health Organization</Author><Year>2011</Year><RecNum>286</RecNum><DisplayText><style face="superscript">29</style></DisplayText><record><rec-number>286</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1436174279">286</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>The World Health Organization,</author></authors></contributors><titles><title>WHO Satement on antenatal care</title><secondary-title> Similarly, higher coverage of birth with a skilled attendant is strongly associated with lower intrapartum SBRs (IPSBR). The median IPSBR is higher for those countries with caesarean section rates below 10%. Across countries with caesarean section rates above 10% there does not appear to be a strong correlation with SBR. This finding is consistent with a recent systematic review in which failed to detect any improvement in maternal or newborn health with caesarean section rates above 10-15% after correcting for “development status”.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CZXRyYW48L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA 32 and are associated with increased risk in subsequent pregnancies for mothers and their offspring.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IeWRlPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj

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bmROb3RlPgB=

ADDIN EN.CITE.DATA 33-35 Policies should encourage appropriate caesarean sections, but more research is required to track and disincentivise “non-medically indicated”intervention.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LaHVucHJhZGl0PC9BdXRob3I+PFllYXI+MjAxMTwvWWVh

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ADDIN EN.CITE.DATA 36 In LMICs much of the caesarean section epidemic is in the private sector, with caesarean rates over 50% in private hospitals, many of which are not medically indicated.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FbCBBcmlmZWVuPC9BdXRob3I+PFllYXI+MjAxNDwvWWVh

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ADDIN EN.CITE.DATA 37Why do stillbirths occur? Many countries, particularly HIC and MICs, collate data on conditions associated with stillbirths. However, given over 55 active classification systems, consistent estimation of stillbirth causation remains difficult even across HICs. ADDIN EN.CITE <EndNote><Cite><Author>Froen</Author><Year>2015</Year><RecNum>147</RecNum><DisplayText><style face="superscript">7,38</style></DisplayText><record><rec-number>147</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434444836">147</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Froen, J. F.</author></authors></contributors><titles><title>Stillbirths: Progress and Unfinished Business</title><secondary-title>Lancet - in press</secondary-title></titles><periodical><full-title>Lancet - in press</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite><Cite><Author>Leisher SH et al</Author><Year>2015</Year><RecNum>199</RecNum><record><rec-number>199</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1435152588">199</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Leisher SH et al,</author></authors></contributors><titles><title>Seeking order amidst chaos: A systematic review of classification systems for causes of stillbirth and neonatal death, 2009-2014</title><secondary-title>BMC Pregnancy &amp; Childbirth (in press)</secondary-title></titles><periodical><full-title>BMC Pregnancy &amp; Childbirth (in press)</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>7,38 In the 2011 Lancet stillbirth series we called for a simplified classification system which could be applied in Low Income Countries (LICs) onto which more detailed categories recorded in other settings could be mapped. ADDIN EN.CITE <EndNote><Cite><Author>Lawn</Author><Year>2011</Year><RecNum>74</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>74</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434442859">74</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lawn, J. E.</author><author>Blencowe, H.</author><author>Pattinson, R.</author><author>Cousens, S.</author><author>Kumar, R.</author><author>Ibiebele, I.</author><author>Gardosi, J.</author><author>Day, L. T.</author><author>Stanton, C.</author></authors></contributors><auth-address>Saving Newborn Lives/Save the Children, Cape Town, South Africa. joylawn@yahoo.co.uk</auth-address><titles><title>Stillbirths: Where? When? Why? How to make the data count?</title><secondary-title>Lancet</secondary-title></titles><periodical><full-title>Lancet</full-title></periodical><pages>1448-63</pages><volume>377</volume><number>9775</number><edition>2011/04/19</edition><keywords><keyword>Cause of Death</keyword><keyword>Data Collection</keyword><keyword>Developed Countries/statistics &amp; numerical data</keyword><keyword>Developing Countries/statistics &amp; numerical data</keyword><keyword>Epidemiologic Measurements</keyword><keyword>Female</keyword><keyword>Fetal Death/classification</keyword><keyword>Humans</keyword><keyword>Maternal Mortality</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy Complications</keyword><keyword>Stillbirth/ epidemiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 23</date></pub-dates></dates><isbn>1474-547X (Electronic)&#xD;0140-6736 (Linking)</isbn><accession-num>21496911</accession-num><urls><related-urls><url>(10)62187-3/abstract</url></related-urls></urls><electronic-resource-num>10.1016/s0140-6736(10)62187-3</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>4 Since 2005, national estimates have been available for all United Nation (UN) member states for neonatal cause of death, ADDIN EN.CITE <EndNote><Cite><Author>Lawn</Author><Year>2012</Year><RecNum>5925</RecNum><DisplayText><style face="superscript">39</style></DisplayText><record><rec-number>5925</rec-number><foreign-keys><key app="EN" db-id="t9dzafrfn95pdie59fc5rtpvza2patwpdvw9">5925</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lawn, J.E.</author><author>Kinney, M.</author><author>Black, R. E.</author><author>Pitt, C.P.</author><author>Cousens, S.</author><author>Kerber, K.</author><author>Corbett, E.</author><author>Moran, A.</author><author>Morrissey, C.</author><author>Oestergaard, M.</author></authors></contributors><titles><title>A decade of change for newborn survival, policy and programmes: a multi-country analysis </title><secondary-title>Health Policy and Planning</secondary-title></titles><periodical><full-title>Health policy and planning</full-title><abbr-1>Health Policy Plan</abbr-1></periodical><pages>In press</pages><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>39 but the lack of similar information for stillbirths limits our ability to act. Even if a new classification system is agreed, there will be a time lag, maybe of a decade, before national estimates are possible for all the major conditions associated with stillbirth.Congenital abnormalities are exceptional in being reported consistently across many stillbirth classification systems. Myths persist that stillbirths are inevitable, and mostly due to non-preventable congenital abnormalities. Yet in most national reports, congenital abnormalities account for <10% all stillbirths after 22 weeks of gestation, with a median of 7.4% and rates well under 1 per 1000 births (Table 2). In settings with limited diagnostics, under-ascertainment of congenital causes is likely, for example non-tertiary hospitals in South Africa (2.5%). Conversely with good diagnostics, where termination of pregnancy (TOP) is illegal a higher proportion is reported (e.g. 21% in Ireland). Furthermore, not all congenital abnormalities are inevitable, e.g. neural tube defect prevention through folic acid supplementation.Babies at greatest riskMales are at 10% higher risk of stillbirth than females. ADDIN EN.CITE <EndNote><Cite><Author>Mondal</Author><Year>2014</Year><RecNum>143</RecNum><DisplayText><style face="superscript">40</style></DisplayText><record><rec-number>143</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434444317">143</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mondal, D.</author><author>Galloway, T. S.</author><author>Bailey, T. C.</author><author>Mathews, F.</author></authors></contributors><auth-address>Biosciences, College of Life and Environmental Sciences, Hatherly Laboratories, University of Exeter, Prince of Wales Road, Exeter EX4 4PS, UK. f.mathews@exeter.ac.uk.</auth-address><titles><title>Elevated risk of stillbirth in males: systematic review and meta-analysis of more than 30 million births</title><secondary-title>BMC Med</secondary-title></titles><periodical><full-title>BMC Med</full-title></periodical><pages>220</pages><volume>12</volume><edition>2014/11/28</edition><keywords><keyword>Adult</keyword><keyword>Female</keyword><keyword>Global Health</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Pregnancy</keyword><keyword>Prospective Studies</keyword><keyword>Risk Factors</keyword><keyword>Sex Factors</keyword><keyword>Stillbirth/ epidemiology</keyword></keywords><dates><year>2014</year></dates><isbn>1741-7015 (Electronic)&#xD;1741-7015 (Linking)</isbn><accession-num>25428603</accession-num><urls><related-urls><url> The likely mechanisms include X-linked congenital conditions and increased risk of preterm labour and poor fetal growth for male babies. This may be related to a higher incidence of placental vascular conditions, including pre-eclampsia. ADDIN EN.CITE <EndNote><Cite><Author>Brown</Author><Year>2015</Year><RecNum>166</RecNum><DisplayText><style face="superscript">41</style></DisplayText><record><rec-number>166</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434457899">166</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Brown, Z. A.</author><author>Schalekamp-Timmermans, S.</author><author>Hofman, A.</author><author>Jaddoe, V.</author><author>Steegers, E.</author></authors></contributors><auth-address>Erasmus Medical Center, Rotterdam, Netherlands.</auth-address><titles><title>[60-OR]: Fetal sex specific differences in maternal vascular adaptation to pregnancy</title><secondary-title>Pregnancy Hypertens</secondary-title></titles><periodical><full-title>Pregnancy Hypertens</full-title></periodical><pages>31-2</pages><volume>5</volume><number>1</number><edition>2015/03/20</edition><dates><year>2015</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>2210-7797 (Electronic)&#xD;2210-7789 (Linking)</isbn><accession-num>25787410</accession-num><urls><related-urls><url>(14)00165-2/abstract</url></related-urls></urls><electronic-resource-num>10.1016/j.preghy.2014.10.064</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>41 The smallest babies face the highest risk of death. Worldwide around 20 million live births are estimated to be low birthweight (<2500g), but this simplistic, dichotomous cut-off fails to differentiate between fetal growth restriction (FGR) and preterm labour, or a combination of the two.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYXR6PC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA 42 There is a higher risk of both antepartum and intrapartum stillbirth among babies experiencing FGR. FGR is often part of a causal network, whereby an already compromised fetus is more susceptible to infection or hypoxic insults. ADDIN EN.CITE <EndNote><Cite><Author>Stanley F</Author><Year>2000</Year><RecNum>146</RecNum><DisplayText><style face="superscript">43</style></DisplayText><record><rec-number>146</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434444573">146</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stanley F, </author><author>Blair E, </author><author>Alberman E.</author></authors></contributors><titles><title>Cerebral palsies: epidemiology and causal pathways. </title><secondary-title>London: Mac Keith</secondary-title></titles><periodical><full-title>London: Mac Keith</full-title></periodical><dates><year>2000</year></dates><urls></urls></record></Cite></EndNote>43 For example the risk of death is higher for those experiencing a hypoxic insult against a background of FGR and infection, and this applies both for stillbirths and liveborn babies who develop neonatal encephalopathy.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GbGVpc3M8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA 44 Where there is high quality obstetric and neonatal care, intrapartum stillbirth is now rare, and hence the majority of stillbirths are antepartum, many with FGR. In these settings, FGR or placental conditions are more likely to be detected and the balance of risks may favour early induction or Caesarean section, hence increasing the preterm birth rate. ADDIN EN.CITE <EndNote><Cite><Author>Delnord</Author><Year>2015</Year><RecNum>3</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434442441">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Delnord, M.</author><author>Blondel, B.</author><author>Zeitlin, J.</author></authors></contributors><auth-address>INSERM U1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Research Center for Epidemiology and Biostatistics Sorbonne Paris Cite (CRESS), Paris Descartes University, Paris, France.</auth-address><titles><title>What contributes to disparities in the preterm birth rate in European countries?</title><secondary-title>Curr Opin Obstet Gynecol</secondary-title></titles><periodical><full-title>Curr Opin Obstet Gynecol</full-title></periodical><pages>133-42</pages><volume>27</volume><number>2</number><edition>2015/02/19</edition><dates><year>2015</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1473-656X (Electronic)&#xD;1040-872X (Linking)</isbn><accession-num>25692506</accession-num><urls><related-urls><url> However early detection of FGR remains a challenge even in HICs. ADDIN EN.CITE <EndNote><Cite><Author>Flenady</Author><Year>2015</Year><RecNum>150</RecNum><DisplayText><style face="superscript">15</style></DisplayText><record><rec-number>150</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434445384">150</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Flenady, V.</author></authors></contributors><titles><title>Stillbirth: A renewed case for action in high-income countries</title><secondary-title>Lancet in press</secondary-title></titles><periodical><full-title>Lancet in press</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>15 Modifiable factors associated with stillbirthWe reviewed potential risk factors for stillbirths including over 35 maternal factors comprising demographic, environmental, nutrition and lifestyle factors, maternal infections and NCDs, and fetal factors (Table 3). We did not include distal determinants of stillbirth such as poverty and inequity, which affect underlying maternal health and access to quality care. Whilst highly important, data were not available to quantify the risk. FGR and preterm labour are frequently a final link in the causal pathway leading to stillbirth, however in this comparative risk factor analysis we focus on the biological risks. Risk ratio data were available for twelve modifiable conditions associated with stillbirth, with prevalence data for all countries (Figure 3, webappendix). These risk factors are not mutually exclusive and many may coincide in the same woman, so the sum of the population attributable risks exceeds 100%. However, comparing categories with the greatest overall impact still provides a useful guide for programmatic priorities towards ending preventable stillbirths.Worldwide, 6.7% (uncertainty: 6.3-7.3%) of stillbirths are attributable to older maternal age (>35 years). Adolescent pregnancy is also associated with increased risk, especially in those under 16. ADDIN EN.CITE <EndNote><Cite><Author>Althabe</Author><Year>2015</Year><RecNum>157</RecNum><DisplayText><style face="superscript">46</style></DisplayText><record><rec-number>157</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434451051">157</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Althabe, F.</author><author>Moore, J. L.</author><author>Gibbons, L.</author><author>Berrueta, M.</author><author>Goudar, S. S.</author><author>Chomba, E.</author><author>Derman, R. J.</author><author>Patel, A.</author><author>Saleem, S.</author><author>Pasha, O.</author><author>Esamai, F.</author><author>Garces, A.</author><author>Liechty, E. A.</author><author>Hambidge, K.</author><author>Krebs, N. F.</author><author>Hibberd, P. L.</author><author>Goldenberg, R. L.</author><author>Koso-Thomas, M.</author><author>Carlo, W. A.</author><author>Cafferata, M. L.</author><author>Buekens, P.</author><author>McClure, E. M.</author></authors></contributors><titles><title>Adverse maternal and perinatal outcomes in adolescent pregnancies: The Global Network&apos;s Maternal Newborn Health Registry study</title><secondary-title>Reprod Health</secondary-title></titles><periodical><full-title>Reprod Health</full-title></periodical><pages>S8</pages><volume>12 Suppl 2</volume><edition>2015/06/13</edition><dates><year>2015</year><pub-dates><date>Jun 8</date></pub-dates></dates><isbn>1742-4755 (Electronic)&#xD;1742-4755 (Linking)</isbn><accession-num>26063350</accession-num><urls></urls><electronic-resource-num>10.1186/1742-4755-12-s2-s8</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>46 We were unable to quantify this risk due to lack of robust age-specific risk data. 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Tm90ZT4A

ADDIN EN.CITE.DATA 47 Such messages must be coupled with access to acceptable family planning methods and empowerment for informed choices.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5VcGFkaHlheTwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+

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ADDIN EN.CITE.DATA 48 Short inter-pregnancy interval is another important risk associated with other poor perinatal outcomes, modifiable with family planning, but the effect on stillbirth is yet to be quantified. ADDIN EN.CITE <EndNote><Cite><Author>Kozuki</Author><Year>2013</Year><RecNum>4</RecNum><DisplayText><style face="superscript">49</style></DisplayText><record><rec-number>4</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434442441">4</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kozuki, N.</author><author>Walker, N.</author></authors></contributors><titles><title>Exploring the association between short/long preceding birth intervals and child mortality: using reference birth interval children of the same mother as comparison</title><secondary-title>BMC Public Health</secondary-title></titles><periodical><full-title>BMC Public Health</full-title></periodical><pages>S6</pages><volume>13 Suppl 3</volume><edition>2014/02/26</edition><keywords><keyword>Birth Intervals/ statistics &amp; numerical data</keyword><keyword>Demography</keyword><keyword>Developing Countries</keyword><keyword>Female</keyword><keyword>Health Status Indicators</keyword><keyword>Health Surveys/statistics &amp; numerical data</keyword><keyword>Humans</keyword><keyword>Infant</keyword><keyword>Infant Mortality/ trends</keyword><keyword>Male</keyword><keyword>Mothers</keyword><keyword>Pregnancy</keyword><keyword>Reference Values</keyword><keyword>Reproductive Health/ statistics &amp; numerical data</keyword><keyword>Risk Factors</keyword><keyword>Socioeconomic Factors</keyword></keywords><dates><year>2013</year></dates><isbn>1471-2458 (Electronic)&#xD;1471-2458 (Linking)</isbn><accession-num>24564713</accession-num><urls><related-urls><url> during pregnancy remain important preventable factors, especially in SSA, although few studies report usable risk data. Improving prevention and treatment of malaria in pregnancy (estimated to be attributable for around 20% of stillbirths in SSA), and syphilis (7.7% (4.6–12.0%) of stillbirths globally, 11.0% (6.7–17.0%) in SSA), should be an important first step in preventing stillbirth in weaker health systems.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYXdrZXM8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxS

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ADDIN EN.CITE.DATA 50,51 It is notable that the campaigns for managing malaria and syphilis in pregnancy have tended to focus on neonatal deaths, despite the associated stillbirth burden being much higher. Data to assess the burden of stillbirths attributable to HIV/AIDS are limited. Based on data from the South African Programme for Identification of Perinatal Priorities we estimate that 0.7% (0.6-0.8%) of stillbirths in SSA may be attributable to HIV infection. The risk may be higher in settings without widespread availability of antiretroviral therapy (webappendix).The global epidemics of obesity and NCDs, notably hypertension and diabetes, are affecting pregnancies in all regions,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OZzwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJlY051

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ZT4A

ADDIN EN.CITE.DATA 52 especially when combined with advanced maternal age. Our estimates suggest that around 10% of stillbirths are attributable to these conditions (Figure 3). Improving outcomes will require efforts aimed both at primary prevention and improved detection and management of affected women, where possible prior to pregnancy. Tobacco has a relatively small PAR (Figure 3), due to a low relative risk and also low prevalence of smoking even in South Asia where smoking has risen dramatically. Over 200,000 stillbirths are attributable to pre-eclampsia and eclampsia (combined PAF 4.7%) with the highest burden in SSA and South Asia. Many of these deaths could be averted with detection and appropriate management in ANC, and improved intrapartum care.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj52b24gRGFkZWxzemVuPC9BdXRob3I+PFllYXI+MjAxMjwv

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ADDIN EN.CITE.DATA 53Pregnancy lasting longer than 42 weeks is associated with an increased risk of stillbirth, accounting for an estimated 14.2% of stillbirths worldwide. Most HICs have introduced policies of induction of labour prior to 42 weeks, with some ecological analyses suggesting substantial impact. ADDIN EN.CITE <EndNote><Cite><Author>Hedegaard</Author><Year>2014</Year><RecNum>5</RecNum><DisplayText><style face="superscript">54</style></DisplayText><record><rec-number>5</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434442441">5</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hedegaard, M.</author><author>Lidegaard, O.</author><author>Skovlund, C. W.</author><author>Morch, L. S.</author><author>Hedegaard, M.</author></authors></contributors><auth-address>Department of Gynecology, Faculty of Health Science, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.&#xD;Department of Obstetrics, Faculty of Health Science, Rigshospitalet, University of Copenhagen, Denmark.</auth-address><titles><title>Reduction in stillbirths at term after new birth induction paradigm: results of a national intervention</title><secondary-title>BMJ Open</secondary-title></titles><periodical><full-title>BMJ Open</full-title></periodical><pages>e005785</pages><volume>4</volume><number>8</number><edition>2014/08/16</edition><keywords><keyword>Epidemiology</keyword><keyword>Obstetrics</keyword></keywords><dates><year>2014</year></dates><isbn>2044-6055 (Electronic)</isbn><accession-num>25125480</accession-num><urls><related-urls><url> This policy could be extended to MIC settings where accurate dating of pregnancies, through early ultrasound, and safe emergency obstetric care are widely available. Caution is needed in settings where these criteria cannot be met and there is real potential for harm to women and their babies.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ib2ZtZXlyPC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48

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ADDIN EN.CITE.DATA 37 For some other important conditions it was not possible to estimate the attributable stillbirths due to lack of prevalence or risk data (webappendix). For example regarding violence against pregnant women, although studies show an increased risk of stillbirth,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYW48L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxSZWNO

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ADDIN EN.CITE.DATA 55,56 and 30% of ever-partnered women experience physical or sexual abuse in their lifetime, there are no prevalence estimates specific to pregnant women. ADDIN EN.CITE <EndNote><Cite><Author>World Health Organization</Author><RecNum>171</RecNum><DisplayText><style face="superscript">57</style></DisplayText><record><rec-number>171</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434464667">171</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>World Health Organization,</author></authors></contributors><titles><title>Global Health Observatory</title><secondary-title> Other factors associated with an increased risk of stillbirth include: bacterial infections (eg chorioamnionitis), viral infections (eg influenza and hepatitis), ADDIN EN.CITE <EndNote><Cite><Author>McClure</Author><Year>2009</Year><RecNum>152</RecNum><DisplayText><style face="superscript">58</style></DisplayText><record><rec-number>152</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434448746">152</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McClure, E. M.</author><author>Goldenberg, R. L.</author></authors></contributors><auth-address>Department of Epidemiology, UNC Global School of Public Health, Chapel Hill, North Carolina, USA. Mcclure@</auth-address><titles><title>Infection and stillbirth</title><secondary-title>Semin Fetal Neonatal Med</secondary-title></titles><periodical><full-title>Semin Fetal Neonatal Med</full-title></periodical><pages>182-9</pages><volume>14</volume><number>4</number><edition>2009/03/17</edition><keywords><keyword>Female</keyword><keyword>Fetal Death/microbiology/virology</keyword><keyword>Humans</keyword><keyword>Infant, Newborn</keyword><keyword>Infection/ complications</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy Complications, Infectious</keyword><keyword>Pregnancy Complications, Parasitic</keyword><keyword>Stillbirth</keyword></keywords><dates><year>2009</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1878-0946 (Electronic)&#xD;1744-165X (Linking)</isbn><accession-num>19285457</accession-num><urls><related-urls><url> other medical conditions such as thyroid disorders and liver disease; ADDIN EN.CITE <EndNote><Cite><Author>Coletta</Author><Year>2010</Year><RecNum>151</RecNum><DisplayText><style face="superscript">59</style></DisplayText><record><rec-number>151</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434448175">151</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Coletta, J.</author><author>Simpson, L. L.</author></authors></contributors><auth-address>Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.</auth-address><titles><title>Maternal medical disease and stillbirth</title><secondary-title>Clin Obstet Gynecol</secondary-title></titles><periodical><full-title>Clin Obstet Gynecol</full-title></periodical><pages>607-16</pages><volume>53</volume><number>3</number><edition>2010/07/28</edition><keywords><keyword>Cholestasis/complications</keyword><keyword>Diabetes Complications</keyword><keyword>Female</keyword><keyword>Fetal Death/etiology/prevention &amp; control</keyword><keyword>Humans</keyword><keyword>Hypertension/complications</keyword><keyword>Kidney Diseases/complications</keyword><keyword>Lupus Erythematosus, Systemic/complications</keyword><keyword>Obesity/complications</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy Complications</keyword><keyword>Stillbirth</keyword><keyword>Thyroid Diseases/complications</keyword></keywords><dates><year>2010</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1532-5520 (Electronic)&#xD;0009-9201 (Linking)</isbn><accession-num>20661045</accession-num><urls></urls><electronic-resource-num>10.1097/GRF.0b013e3181eb2ca0</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>59 and indoor air pollution (30% increased risk).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbWVnYWg8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA 60,61High quality ANC could identify and address many of these conditions. Currently over half of pregnant women are estimated to attend at least four ANC visits. ADDIN EN.CITE <EndNote><Cite><Author>UNICEF</Author><Year>2015</Year><RecNum>266</RecNum><DisplayText><style face="superscript">62</style></DisplayText><record><rec-number>266</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1435584407">266</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>UNICEF,</author></authors></contributors><titles><title>Progress for Children. Beyond averages: Learning from the MDGs. However, there is a need to optimise timing and quality and reach the marginalised, including those with mental health conditions.PEVuZE5vdGU+PENpdGU+PFllYXI+MjAxMTwvWWVhcj48UmVjTnVtPjY8L1JlY051bT48RGlzcGxh

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ADDIN EN.CITE.DATA 63,64 Whilst these biomedical conditions are important and must be addressed in order to improve fetal and maternal health, especially in LMIC, the common factor for many stillbirths is the absence or low quality of intrapartum care, including access to timely referral.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HZWVsaG9lZDwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+

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ADDIN EN.CITE.DATA 65,66 This must be urgently addressed. It is clear that progress in preventing stillbirths will require working with groups who focus on issues beyond maternal and newborn care, notably family planning, NCDs, nutrition, and malaria and other infections, as well as wider health systems change, plus strategies for women’s education, empowerment and community engagement including with men, mother-in-laws and other societal gatekeepers.Counting stillbirths and making the data countSome progress has been made in measurement since the 2011 Lancet Stillbirth Series (webappendix). Stillbirths are increasingly counted, which may be partly related to more visible SBR estimates and rankings. ADDIN EN.CITE <EndNote><Cite><Author>Cousens</Author><Year>2011</Year><RecNum>71</RecNum><DisplayText><style face="superscript">6</style></DisplayText><record><rec-number>71</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434442859">71</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cousens, S.</author><author>Blencowe, H.</author><author>Stanton, C.</author><author>Chou, D.</author><author>Ahmed, S.</author><author>Steinhardt, L.</author><author>Creanga, A. A.</author><author>Tuncalp, O.</author><author>Balsara, Z. P.</author><author>Gupta, S.</author><author>Say, L.</author><author>Lawn, J. E.</author></authors></contributors><auth-address>London School of Hygiene and Tropical Medicine, London, UK. simon.cousens@lshtm.ac.uk</auth-address><titles><title>National, regional, and worldwide estimates of stillbirth rates in 2009 with trends since 1995: a systematic analysis</title><secondary-title>Lancet</secondary-title></titles><periodical><full-title>Lancet</full-title></periodical><pages>1319-30</pages><volume>377</volume><number>9774</number><edition>2011/04/19</edition><keywords><keyword>Female</keyword><keyword>Global Health</keyword><keyword>Humans</keyword><keyword>Models, Statistical</keyword><keyword>Pregnancy</keyword><keyword>Stillbirth/ epidemiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 16</date></pub-dates></dates><isbn>1474-547X (Electronic)&#xD;0140-6736 (Linking)</isbn><accession-num>21496917</accession-num><urls><related-urls><url>(10)62310-0/abstract</url></related-urls></urls><electronic-resource-num>10.1016/s0140-6736(10)62310-0</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>6 More data are available for SBRs, with the number of countries with no data reduced from 68 to 38. However, amongst those with data, 81 do not have nationally representative data and more do not have trend data. In many settings stillbirths are infrequently weighed at birth, especially for births occurring outside of health facilities. Shifting the stillbirth definition to one based on GA should further increase data quality and comparability, recognising further advances are needed in GA accuracy (panel 1). Whilst SBR data have increased, data gaps remain for IPSBR and over 130 countries are without available data, despite being recorded in most routine labour ward registries. It should be a scandal that an estimated 1.3 million intrapartum stillbirths, the majority of which are preventable, are not collated in hospital or national information systems. Improving data will require investments in national health information systems, as promoted by the “Measurement and Accountability for results” roadmap, which is crosscutting, and the ENAP measurement improvement roadmap which focuses on newborns and stillbirths.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Nb3hvbiBTRzwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+

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ADDIN EN.CITE.DATA 67,68 As part of ENAP, WHO is developing perinatal audit tools to assist in addressing modifiable factors, ADDIN EN.CITE <EndNote><Cite><Author>Kerber K J</Author><Year>2015</Year><RecNum>182</RecNum><DisplayText><style face="superscript">69</style></DisplayText><record><rec-number>182</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1435091381">182</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kerber K J, </author><author>Mathai M, </author><author>Lewis G, </author><author>Flenady V, </author><author>Erwich JJ HM, </author><author>Segun T, </author><author>Aliganyira P, </author><author>Abdelmegeid A, </author><author>Allanson E, </author><author>Roos N, </author><author>Rhoda N, </author><author>Lawn J E, </author><author>Pattinson R. </author></authors></contributors><titles><title>Every Woman, Every Newborn (Paper 9): Counting every stillbirth and neonatal death to improve quality of care for every pregnant woman and her baby</title><secondary-title>BMC Pregnancy and Childbirth (in press)</secondary-title></titles><periodical><full-title>BMC Pregnancy and Childbirth (in press)</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>69 and to link with a minimum perinatal dataset. ADDIN EN.CITE <EndNote><Cite><Author>Froen</Author><Year>2015</Year><RecNum>147</RecNum><DisplayText><style face="superscript">7</style></DisplayText><record><rec-number>147</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434444836">147</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Froen, J. F.</author></authors></contributors><titles><title>Stillbirths: Progress and Unfinished Business</title><secondary-title>Lancet - in press</secondary-title></titles><periodical><full-title>Lancet - in press</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>7 These initiatives provide opportunities to develop better tools which can be applied to address important research questions. However, investment is needed in high burden countries to operationalise this.All babies should be registered at birth. Birth registration now covers two-thirds of the world’s livebirths, but <5% of stillbirths. Coverage of death registration is even lower, covering <5% of neonatal deaths and even fewer stillbirths. Recording all facility births, stillbirths (especially intrapartum) and newborn, child and maternal deaths using standard definitions is feasible, and linking these to birth registration would rapidly increase SBR data availability, even by 2020. The inclusion of gestational age, birth weight and associated maternal conditions on death certificates would greatly increase data utility allowing cross-tabulation of maternal and perinatal conditions. Including these data on birth certificates would provide important intergenerational information on health such as NCD outcomes. ADDIN EN.CITE <EndNote><Cite><Author>Froen</Author><Year>2015</Year><RecNum>147</RecNum><DisplayText><style face="superscript">7</style></DisplayText><record><rec-number>147</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434444836">147</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Froen, J. F.</author></authors></contributors><titles><title>Stillbirths: Progress and Unfinished Business</title><secondary-title>Lancet - in press</secondary-title></titles><periodical><full-title>Lancet - in press</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>7Accelerating progress to end preventable stillbirths requires improved data. Little investment has yet been made in improving coverage data for interventions that improve maternal and newborn health. This is an urgent priority and should include tracking content and quality of interventions specific to stillbirth prevention, particularly within ANC and intrapartum care.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcnljZTwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJl

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ADDIN EN.CITE.DATA 70 For example coverage data for syphilis detection and treatment, components of advanced ANC, and intrapartum monitoring remain absent in most countries, and in global tracking. In addition, data are needed regarding reduction of stigma and provision of bereavement care. ADDIN EN.CITE <EndNote><Cite><Author>Flenady</Author><Year>2015</Year><RecNum>150</RecNum><DisplayText><style face="superscript">15</style></DisplayText><record><rec-number>150</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434445384">150</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Flenady, V.</author></authors></contributors><titles><title>Stillbirth: A renewed case for action in high-income countries</title><secondary-title>Lancet in press</secondary-title></titles><periodical><full-title>Lancet in press</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>15 The 2011 Lancet Stillbirth Series ranked research priorities for improving our understanding of stillbirth epidemiology (webappendix). ADDIN EN.CITE <EndNote><Cite><Author>Lawn</Author><Year>2011</Year><RecNum>74</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>74</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434442859">74</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lawn, J. E.</author><author>Blencowe, H.</author><author>Pattinson, R.</author><author>Cousens, S.</author><author>Kumar, R.</author><author>Ibiebele, I.</author><author>Gardosi, J.</author><author>Day, L. T.</author><author>Stanton, C.</author></authors></contributors><auth-address>Saving Newborn Lives/Save the Children, Cape Town, South Africa. joylawn@yahoo.co.uk</auth-address><titles><title>Stillbirths: Where? When? Why? How to make the data count?</title><secondary-title>Lancet</secondary-title></titles><periodical><full-title>Lancet</full-title></periodical><pages>1448-63</pages><volume>377</volume><number>9775</number><edition>2011/04/19</edition><keywords><keyword>Cause of Death</keyword><keyword>Data Collection</keyword><keyword>Developed Countries/statistics &amp; numerical data</keyword><keyword>Developing Countries/statistics &amp; numerical data</keyword><keyword>Epidemiologic Measurements</keyword><keyword>Female</keyword><keyword>Fetal Death/classification</keyword><keyword>Humans</keyword><keyword>Maternal Mortality</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy Complications</keyword><keyword>Stillbirth/ epidemiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 23</date></pub-dates></dates><isbn>1474-547X (Electronic)&#xD;0140-6736 (Linking)</isbn><accession-num>21496911</accession-num><urls><related-urls><url>(10)62187-3/abstract</url></related-urls></urls><electronic-resource-num>10.1016/s0140-6736(10)62187-3</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>4 The top five priorities centred on risk factors, and our review and analysis underline limited progress made on this knowledge base, even for conditions such as malaria and HIV (and new ones such as Ebola) with major investment but where SBR or IPSBR data are rarely collected. Household surveys, a potentially important source of data in countries lacking robust routine data collection systems, remain problematic for SBR capture, but no research to address this issue is ongoing. Methodological research is needed to address this issue, including improved understanding of which survey-based tools (e.g. birth history, pregnancy-history, truncated pregnancy-history) maximise the capture of stillbirths, and how these can be best implemented. Demographic surveillance sites such as the INDEPTH network provide a unique opportunity to test retrospective survey modules against prospective pregnancy capture data, and also assess the length of interviews which is a major constraint in DHS given the questionnaire already has long, complex questions. Regarding classifying causes-of-stillbirth, the greatest challenge remains the development of a practical standardised classification system which is effective with varying complexity of data from verbal autopsy to clinical attribution possible in facilities to centres with more extensive laboratory testing. ADDIN EN.CITE <EndNote><Cite><Author>Lawn</Author><Year>2010</Year><RecNum>99</RecNum><DisplayText><style face="superscript">71</style></DisplayText><record><rec-number>99</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434442859">99</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lawn, J. E.</author><author>Gravett, M. G.</author><author>Nunes, T. M.</author><author>Rubens, C. E.</author><author>Stanton, C.</author></authors></contributors><auth-address>Saving Newborn Lives/Save the Children, 11 South Way, Pinelands Cape Town, South Africa.</auth-address><titles><title>Global report on preterm birth and stillbirth (1 of 7): definitions, description of the burden and opportunities to improve data</title><secondary-title>BMC Pregnancy Childbirth</secondary-title></titles><periodical><full-title>BMC Pregnancy Childbirth</full-title></periodical><pages>S1</pages><volume>10 Suppl 1</volume><edition>2010/03/27</edition><keywords><keyword>Cause of Death</keyword><keyword>Data Collection/standards</keyword><keyword>Female</keyword><keyword>Fetal Death/epidemiology</keyword><keyword>Global Health</keyword><keyword>Humans</keyword><keyword>Infant Mortality</keyword><keyword>Infant, Newborn</keyword><keyword>Pregnancy</keyword><keyword>Premature Birth/ epidemiology</keyword><keyword>Prevalence</keyword><keyword>Stillbirth/ epidemiology</keyword></keywords><dates><year>2010</year></dates><isbn>1471-2393 (Electronic)&#xD;1471-2393 (Linking)</isbn><accession-num>20233382</accession-num><urls><related-urls><url> WHO is working on this issue. 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ADDIN EN.CITE.DATA 72,73 The commonly used WHO verbal autopsy tool, while retaining questions on the timing of stillbirth (fresh/ macerated), no longer includes questions on the causes of stillbirth.In each region of the world the fastest progressing country for SBR (Figure 1B, web appendix) also tended to make more progress than their neighbours in data improvement. For example Rwanda has increased birth registration and notably increased reporting of the baby’s birth weight from under a third to over two-thirds (webappendix).ConclusionAs we transition from the MDG to the SDG-era, the global architecture for accountability for health outcomes is more complex. Ending preventable deaths of newborns and under-five children by 2030 is a sub-target under SDG3 (the only health goal), with 16 other goals focused mainly on social and economic development and the environment. The discourse has shifted from health being essential for development, to development being necessary to improve health. Neonatal mortality is now an explicit SDG target. Many countries requested that WHO establish an explicit stillbirth target, which is why this was included in ENAP.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYXduPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA 3 Opportunities exist, with more investment planned for national health information systems, including CRVS, and ongoing calls for more use of data for accountability, but there is a pressing need for leadership to include stillbirths at a global level, especially in high burden countries. ADDIN EN.CITE <EndNote><Cite><Author>L</Author><Year>2015</Year><RecNum>149</RecNum><DisplayText><style face="superscript">7,74</style></DisplayText><record><rec-number>149</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434445269">149</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>De Bernis L,</author></authors></contributors><titles><title>Stillbirths: ending preventable deaths by 2030</title><secondary-title>Lancet submitted</secondary-title></titles><periodical><full-title>Lancet submitted</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite><Cite><Author>Froen</Author><Year>2015</Year><RecNum>147</RecNum><record><rec-number>147</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434444836">147</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Froen, J. F.</author></authors></contributors><titles><title>Stillbirths: Progress and Unfinished Business</title><secondary-title>Lancet - in press</secondary-title></titles><periodical><full-title>Lancet - in press</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>7,74 Leadership is needed at all levels, but it will be critical to have technical skills to improve and use programmatic data to close quality and equity gaps. This will require intentional investment in effective data systems and skills-building in communities most affected by stillbirth, including affected women. ADDIN EN.CITE <EndNote><Cite><Author>L</Author><Year>2015</Year><RecNum>149</RecNum><DisplayText><style face="superscript">74</style></DisplayText><record><rec-number>149</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434445269">149</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>De Bernis L,</author></authors></contributors><titles><title>Stillbirths: ending preventable deaths by 2030</title><secondary-title>Lancet submitted</secondary-title></titles><periodical><full-title>Lancet submitted</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>74 Household surveys have been strengthened to improve the capture of neonatal and child deaths; this can also be done for stillbirth. At all health facilities, we call for systematic recording of stillbirths especially intrapartum stillbirth, with collation and review of these data at both a local and national level, such as through perinatal audit. The majority of stillbirths, particularly intrapartum stillbirths, are preventable and those due to syphilis and malaria should be considered unacceptable even in the weakest health systems. Improving data will not alone lead to change, but provides accountability for targeting interventions, reaching the more than 7500 women every day all over the world who experience the reality of stillbirth. We call for a joint programmatic and measurement agenda that includes mothers, newborns and stillbirths, in order to end all these preventable deaths. For The Lancet Ending Preventable Stillbirths Series study group (J Frederik Fr?en, Joy E Lawn, Alexander Heazell, Vicki J Flenady, Mary Kinney, Luc de Bernis, Hannah Blencowe, Susannah Hopkins Leisher)With The Lancet Stillbirth Epidemiology Investigator GroupJun Zhu, Juan Liang, Yi Mu, Xiaohong Li (National Office for Maternal and Child Health Surveillance of China, West China Second University Hospital); Anthony Costello, Tim Colbourn, Edward Fottrell, Audrey Prost, David Osrin, Carina King, Melissa Neuman (University College London (Institute for Global Health), Women Group’s trials: Bangladesh-PCP, Ekjut-India, India - Society for Nutrition, Education and Health Action, Nepal-Dhanusha, Nepal-Makwanpur, Malawi-MaiMwana, Malawi-MaiKhanda); Neena Shah More (Society for Nutrition, Education and Health Action, Mumbai, India) Kishwar Azad (Diabetic Association of Bangladesh Perinatal Care Project, Bangladesh); Dharma Manandhar (Mother and Infant Research Association (MIRA), Nepal); Nirmala Nair, Prasanta Tripathy (Ekjut, India); Rajesh Kumar, Ariarathinam Newtonraj , Manmeet Kaur, Madhu Gupta (Department of Community Medicine, School of Public Health, Post Graduate Institute of Medical Education and Research, Chandigarh, India); Aimable Musafili (Uppsala University); Beena Varghese (Public Health Foundation of India ); Robert Pattison (South African Medical Research Council, Maternal and Infant Health Care Strategies Unit); Jane Hirst (University of Oxford ); Peter Waiswa (INDEPTH network- Maternal Newborn Working Group; Makerere University); Daniel Kadobera (Iganga HDSS); Sanni Kujala (Iganga HDSS; Swedish Organization for Global Health); Anna Bergstrom (NeoKip study; Karolinska Institute); Tambosi Phiri, Jennifer A Hall (University College London (Institute for Global Health), MaiMwana, Malawi); Louise Day, Stacy L Saha, Shafiul Alam (MIS-Research Department, LAMB, Bangladesh); Anisur Rahman , Shams El-Arifeen (iccdr-b); Sayed Rubayet (Save the Children); Ahmed Ali Hassan (Sudan Stillbirth Society and former MSF staff); Lucy Smith, Bradley N Manktelow, Elizabeth S Draper (University of Leicester, MBRRACE-UK); Nanbert Zhong (Peking University Center of Medical Genetics, New York State Institute for Basic Research in Developmental Disabilities); Jans Langhoff-Roos (University of Copenhagen); Vicki Flenady (Mater University); K?rt Allvee (Estonian Birth and Abortion Registries); Mika Gissler (THL National Institute for Health and Welfare, Finland); Nicholas Lack (Germany); Sonam Wangdi (Ministry of Health Bhutan); Jan Cap, Zuzana Podmanicka (Statistics Slovakia); Katarzyna Szamotulska (Poland); Chantal Hukkelhoven, Joyce Dijs-Elsinga (The Netherlands Perinatal Registry); Theopisti Kyprianou (Statistical Office Ministry of Health Cyprus); Kari Klungs?yr ( The Medical Birth Registry of Norway, Norwegian Institute of Public Health); Flor de Maria Herandez (Instituto Nacional de Estadistica, Guatemala); Ala Curteneau (Mother and Child Institute, Chisinau, Republic of Moldova); Henrique Barros, Sofia Correia (Epidemiology Research Unit (EPIUnit) - Institute of Public Health?,?University of Porto, Portugal); Shorena Tsiklauri (GEOSTAT); Ellen Lundqvist (National Board of Health and Welfare, Sweden); Tinga Fulbert Ilboudo (DHIS2 – Burkina Faso); Abdouli Bah, Lamin Jawara (HMIS Gambia); Jennifer Zeitlin (EUROPERISTAT); Jelena Isakova (Health Information Centre, Institute of Hygiene, Lithuania), Olav Poppe (World Health Organization/ DHIS 2).ContributionsJoy E Lawn, Hannah Blencowe, (overall coordination, SBRs, IPSBRs, cause of death, RF analysis) and Simon Cousens overall statistical advice. Zeshan Qureshi (IPSBR and SBR data published studies searches and abstraction)Suhail Shiekh (registry data review). Claire Calderwood (IPSBR combined databases and risk factor reviews/abstraction) Fiorella Bianchi Jassir (Fastest progressor analysis). All the authors reviewed and input to the manuscript. The content of this Series paper does not necessarily indicate the view of the authors’ organisations.Conflicts of interestWe declare that we have no conflicts of interest. AcknowledgementsWe are grateful to the staff of the General Bureau of Statistics of Suriname, Malaysian National Statistical Office, Central Informatics Organisation of Bahrain, Turkisk Statistical Institute, National Statistical Committee Belarus, INEGI (Mexico), INEC (Costa Rica), and INE (Chile) for their assistance in responding to queries in their country’s SBR data. We are grateful to Josh Vogel and the WHO Multi-Country Survey on Maternal and Newborn Health Research Network for their assistance in re-analysing the stillbirth rate data from the WHO Global Survey on Maternal and Perinatal Health and WHO Multi-country Survey on Maternal and Newborn Health.Funding statement:No specific funding was received for the Lancet stillbirth series but the time of HB and JEL for the stillbirth rate estimates was funded by the Bill & Melinda Gates Foundation through Save the Children’s Saving Newborn Lives programme. The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. ADDIN EN.REFLIST References1.UN Inter-agency Group for Child Mortality Estimation (UN-IGME). Levels and Trends in Child Mortality. 2014.2.Darmstadt GL, Kinney MV, Chopra M, et al. Who has been caring for the baby? Lancet 2014; 384(9938): 174-88.3.Lawn JE, Blencowe H, Oza S, et al. 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Global report on preterm birth and stillbirth (1 of 7): definitions, description of the burden and opportunities to improve data. BMC Pregnancy Childbirth 2010; 10 Suppl 1: S1.72.Vergnano S, Fottrell E, Osrin D, et al. Adaptation of a probabilistic method (InterVA) of verbal autopsy to improve the interpretation of cause of stillbirth and neonatal death in Malawi, Nepal, and Zimbabwe. Popul Health Metr 2011; 9: 48.73.Bapat U, Alcock G, More NS, Das S, Joshi W, Osrin D. Stillbirths and newborn deaths in slum settlements in Mumbai, India: a prospective verbal autopsy study. BMC Pregnancy Childbirth 2012; 12: 39.74.De Bernis L. Stillbirths: ending preventable deaths by 2030. Lancet submitted 2015.75.Genest DR, Singer DB. Estimating the time of death in stillborn fetuses: III. External fetal examination; a study of 86 stillborns. Obstet Gynecol 1992; 80(4): 593-600.76.Gold KJ, Abdul-Mumin AR, Boggs ME, Opare-Addo HS, Lieberman RW. Assessment of "fresh" versus "macerated" as accurate markers of time since intrauterine fetal demise in low-income countries. Int J Gynaecol Obstet 2014; 125(3): 223-7.Panel 1 Defining stillbirth and intrapartum stillbirthFetal loss and stillbirthInternational Classification of Disease 10th revision (ICD 10) definitions (note birth weight was given priority over gestational age (GA))late fetal death ≥1000 gms or ≥28 weeks or ≥35cmearly fetal death ≥500 gms or ≥22 weeks or ≥25cmmiscarriage as a pregnancy loss before 22 completed weeks of GAWorld Health Organization (WHO) definitions For international comparison WHO uses stillbirth to mean the ICD definitions of late fetal deaths (ie ≥1000gms with an assumed equivalent of 28 weeks gestation).However the birthweight and GA thresholds do not give equivalent results. For example in the US if stillbirths were defined by ≥500gm birthweight definition, the stillbirth rate (SBR) is lower by 40% than using the at 22 week definition, and if ≥1000gm then is lower by 21% than the 28 weeks definition. ADDIN EN.CITE <EndNote><Cite><Author>Blencowe</Author><Year>2015</Year><RecNum>137</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>137</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1439912058">137</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Blencowe, H,</author><author>Cousens S, </author><author>Bianchi Jassir F, </author><author>Say L, </author><author>Chou D, </author><author>Mathers C, </author><author>Hogan D, </author><author>Shiekh S, </author><author>Qureshi ZU, </author><author>You D, </author><author>Lawn JE,</author><author>For the Lancet Stillbirth investigator group.</author></authors></contributors><titles><title>National, regional and worldwide estimates of stillbirth rates in 2015, with trends from 2000</title><secondary-title>submitted to Lancet Global Health</secondary-title></titles><periodical><full-title>submitted to Lancet Global Health</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>16 Hence the definition should be based on one parameter and we propose that a GA threshold is most appropriate as it is a better predictor of viability than birthweight and Information of gestational age is more widely available than birthweight for many stillbirths. In many Low-Middle income countries GA is primarily based on last menstrual period, and improving GA accuracy in these settings requires additional innovation but is more feasible than weighing all stillbirths at home.For these stillbirth rate estimates, we use the >28 weeks definition, which represents third trimester stillbirths and hence undercounts the true burden if early stillbirths were included. We use the term stillbirth to refer to all early and late fetal deaths since ICD and many countries do count early stillbirths, mostly from 22 weeks.Intrapartum stillbirthAn intrapartum stillbirth is a death which occurs after the onset of labour but before birth. Diagnosis of intrapartum stillbirth requires confirmation of the presence of a fetal heart rate at the onset of labour. In settings where fetal heart rate monitoring is lacking, examination of the skin appearance is frequently used to estimate the timing of the stillbirth. Signs of skin maceration begin at 6 – 12 hours after fetal death, and a “fresh” skin appearance with no signs of maceration is considered a surrogate measure for intrapartum stillbirth. ADDIN EN.CITE <EndNote><Cite><Author>Genest</Author><Year>1992</Year><RecNum>9</RecNum><DisplayText><style face="superscript">75</style></DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1434442441">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Genest, D. R.</author><author>Singer, D. B.</author></authors></contributors><auth-address>Department of Pathology, Brigham and Women&apos;s Hospital, Boston, Massachusetts.</auth-address><titles><title>Estimating the time of death in stillborn fetuses: III. External fetal examination; a study of 86 stillborns</title><secondary-title>Obstet Gynecol</secondary-title></titles><periodical><full-title>Obstet Gynecol</full-title></periodical><pages>593-600</pages><volume>80</volume><number>4</number><edition>1992/10/01</edition><keywords><keyword>Autopsy</keyword><keyword>Female</keyword><keyword>Fetal Death/ pathology</keyword><keyword>Gestational Age</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Observer Variation</keyword><keyword>Predictive Value of Tests</keyword><keyword>Reproducibility of Results</keyword><keyword>Retrospective Studies</keyword><keyword>Skin/ pathology</keyword><keyword>Skin Pigmentation</keyword><keyword>Time Factors</keyword></keywords><dates><year>1992</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0029-7844 (Print)&#xD;0029-7844 (Linking)</isbn><accession-num>1407878</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>75 However this may be unreliable and can underestimate intrapartum stillbirth, especially where fetal death during labour occurs at home, and delays in access to care are more than 6 – 12 hours.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Hb2xkPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA 76 The intrapartum or fresh SBR is a useful marker of stillbirths that may be preventable due to improved care during labour, however it might be an over estimate as it will include babies with underlying conditions, such as FGR, infections or congenital abnormalities. For programmatic action, where possible the intrapartum stillbirth rate should be calculated, excluding those with severe congenital abnormalities, as antenatal diagnosis of these will affect the level of intervention during labour.See web appendix A1 for details of relevant time periods and definitions of related birth outcomes Panel 2 Overview of data inputs and methods Stillbirth rates Inputs Stillbirth rate (SBR) data were identified through web-based searches of National Statistical Office and Ministry of Health websites of all countries. In addition, for countries outside the Millennium Development Goal Developed region, systematic searches were undertaken, covering the published literature and all Demographic and Reproductive Health Surveys. A Stillbirth Epidemiology Investigator group was created, with calls for data distributed via relevant groups and list serves and individual PIs approached. Data were assessed using specified inclusion criteria, and were adjusted to the ≥28 week definition where required. 157 countries in total contributed data. High quality Civil Registration and Vital Statistics (CRVS) data were available from 54 countries, lower quality CRVS or Health Management Information Systems (HMIS) data from 60 countries. In addition, 127 retrospective household surveys were included (57 countries) and 329 studies from 57 countries. Stillbirth estimationFor 31 countries, with “complete” time series high quality national data the country’s own reported rates, adjusted where necessary (see above), were smoothed with loess regression to produce estimated trends for 2000-2015.For 164 countries without high quality time-series CRVS data, a regression model was developed to predict national stillbirth rates using stillbirth rate data identified from all countries meeting the inclusion criteria. For 164 countries without recent, national high quality SBR data, their subnational or other data were included as inputs, and national predictor covariates were used to model 2015 estimates and time trends. The final model included ln(nmr), ln(gni), ln(lbw), mean years of adult female education, the context of the study and the region as the main variables for prediction purposes. Details are given elsewhere. ADDIN EN.CITE <EndNote><Cite><Author>Blencowe</Author><Year>2015</Year><RecNum>137</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>137</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1439912058">137</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Blencowe, H,</author><author>Cousens S, </author><author>Bianchi Jassir F, </author><author>Say L, </author><author>Chou D, </author><author>Mathers C, </author><author>Hogan D, </author><author>Shiekh S, </author><author>Qureshi ZU, </author><author>You D, </author><author>Lawn JE,</author><author>For the Lancet Stillbirth investigator group.</author></authors></contributors><titles><title>National, regional and worldwide estimates of stillbirth rates in 2015, with trends from 2000</title><secondary-title>submitted to Lancet Global Health</secondary-title></titles><periodical><full-title>submitted to Lancet Global Health</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>16Projections to 2030 at national level were based on trends for SBR 2000– 2015, assuming the same national ARR, and combining with UN PopDivision medium birth cohort projections by country by year, to estimate rates and numbers for each country, region and globally to 2030.UncertaintyUncertainty estimates were derived using a bootstrap approach by drawing 1000 bootstrap samples with replacement from the input data and re-running the model to produce estimates and taking the 2.5 and 97.5 percentile values for each cause as the uncertainty bounds. For countries with high quality time-series data where reported rates were used we assumed a Poisson distribution. ADDIN EN.CITE <EndNote><Cite><Author>Blencowe</Author><Year>2015</Year><RecNum>137</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>137</rec-number><foreign-keys><key app="EN" db-id="fwxdwse0cvt00zez5zrpap0kzpspp02fsdzs" timestamp="1439912058">137</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Blencowe, H,</author><author>Cousens S, </author><author>Bianchi Jassir F, </author><author>Say L, </author><author>Chou D, </author><author>Mathers C, </author><author>Hogan D, </author><author>Shiekh S, </author><author>Qureshi ZU, </author><author>You D, </author><author>Lawn JE,</author><author>For the Lancet Stillbirth investigator group.</author></authors></contributors><titles><title>National, regional and worldwide estimates of stillbirth rates in 2015, with trends from 2000</title><secondary-title>submitted to Lancet Global Health</secondary-title></titles><periodical><full-title>submitted to Lancet Global Health</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>16Intrapartum stillbirth rates InputsData on intrapartum stillbirths were identified through web-based searches of National Statistical Office and Ministry of Health websites and systematic literature searches for all countries. Further data were requested from the Stillbirth Epidemiology Investigator group. Data were assessed using specified inclusion/ exclusion criteria. Where CRVS and routine data were available for more than one year, the latest full year of data availability was used. Data were included from 65 countries (41 outside the developed region). This included 173 data points covering over 37 million births with 1.1 million stillbirths. EstimationVarious strategies to fit a regression model to estimate the national intrapartum stillbirth rate were attempted, including approaches to predict intrapartum stillbirth rate, the proportion of all stillbirths that are intrapartum and the logodds of stillbirth (see webappendix). In view of data limitations it was not possible to identify a satisfactory model. Therefore to estimate the intrapartum stillbirth rate for each country we first calculated the median proportion of stillbirths that are intrapartum from all data inputs from a given region. For all countries in a given MDG region the intrapartum stillbirth rate was estimated by applying the regional median to the country estimated stillbirth rate for 2015. UncertaintyUncertainty estimates for the proportion of stillbirths that are intrapartum were derived by the use of regional IQR for regions with more than 10 data inputs. For regions with 10 or fewer data points, the upper and lower datapoints were used. We simulated uncertainty estimates for intrapartum stillbirth rates by using 1000 independent random draws of the uncertainty around the total stillbirth estimated for the proportion of total stillbirths that were intrapartum.Congenital conditions associated with stillbirthInputsA web-based search of National Statistical Office and Ministry of Health websites of all countries was undertaken to identify databases and reports providing data on cause of death for stillbirths was undertaken. National data were available from 22 countries. Data were excluded when countries reported with an early stillbirth definition (≥20 weeks or ≥22 weeks) and included terminations of pregnancy or did not provide consistent data on all stillbirths (Italy had data on <50% of stillbirths and >25% garbage codes (deaths assigned to ill-defined causes that are not useful for public health analyses)); Philippines only reported on the top 10 causes of stillbirth (which included 74% of all stillbirths)). Data on were abstracted regarding the definition of stillbirth used, the proportion of stillbirths where a congenital abnormality was associated with the stillbirth, and the proportion of stillbirths with no cause recorded. Data regarding the current status of screening and the legal status of Termination of Pregnancy for congenital abnormalities was abstracted from these reports, and supplemented by web-based searches where necessary.Risk factor analyses for stillbirthInputsWe undertook a review of the literature to identify potentially modifiable risk factors associated with stillbirth reported in the published literature. We grouped these risk factors into the following categories: 1) Maternal - demographic/ fertility related, infection, nutrition, lifestyle, non-communicable disease, environmental; and 2) Fetal. (Table 2)We prioritized inclusion of risk factors with strong evidence of an association with stillbirth, and available prevalence data on the exposure for countries from all worldwide regions. Recent systematic reviews (published 2010 – 2015) were searched for data to inform the risk associations. We included studies with median data collection from 1995, restricting to more recent data were possible. Data on the population prevalence of the risk factor by country were searched from publically available databases. (see webappendix) For important potentially modifiable exposures with available prevalence data, but with no risk association data from recent systematic reviews, further systematic reviews were undertaken. Estimation processFor included conditions, we calculated the proportion of cases in the whole population that may be attributed to the exposure (population attributable fraction (PAF)). PAF is the proportional reduction in stillbirth that would occur if exposure to a risk factor were reduced to an alternative ideal comparative scenario (the counterfactual e.g. no active syphilis in pregnancy). However, as stillbirths may be cause by multiple risk factors, and individual risk factors may interact in their impact on overall risk of stillbirth, PAFs for individual risk factors overlap. This calculation assumes causality and complete control of possible confounding factors, and hence will over-estimate the effect.UncertaintyWe quantified uncertainty around these estimates by taking 1000 random draws of the national number of stillbirths and the risk associated with the condition, and the prevalence of the risk factor (where available), assuming a normal distribution with mean equal to the point estimate of the parameter and the standard deviation equal to the estimated standard error. We summed these data at the regional level for each draw and present the 2.5th and 97.5th percentiles of the resulting distributions as the uncertainty range. See Webappendix for more details of inputs and methodsFigure 1: Projections of progress for stillbirth rates at global and regional levelProjections to 2030 for the national stillbirth rate targets of 12 or less per 1000 total births as set in the Every Newborn Action Plan 1841562865B: Variation in national average annual rates of reduction of stillbirth rates (2000 – 2015), showing the fastest progressing country in each Millennium Development Goal region 1841530480See web appendix for details and Blencowe et al for details of stillbirth rate estimatesC. Time for each region to reach the same stillbirth rate as high-income countries in 2015, based on ARR from 2000–201505744210Figure 2: Regional variation in estimated stillbirth rates, showing uncertainty ranges, and the proportion of intrapartum stillbirths for 201566294035560?TOTALDeveloped regionEastern AsiaLatin AmericaCaucasus and Central AsiaSouth-eastern AsiaN.Africa and W.AsiaSouthern AsiaSub-Saharan Africaand CaribbeanEstimated stillbirth rate per 1000 total births(uncertainty range)18.9(17.4 - 21.1)3.3(3.2 - 3.4)7.3(5.6 - 10.3)8.6(8.0 - 9.6)11.7(9.9 – 14.4)13.5(11.8 - 15.7)14.7(13.3 - 16.5)26.3(23.5 - 29.6)29.4(26.0 - 35.0)Number of stillbirths2,682,00047,000139,40094,50020,600157,100131,300988,1001,103,900Estimated intrapartum stillbirths (%)49.6%10.0%19.9%16.8%19.9%45.7%42.0%59.3%51.1%Percentage of stillbirths in rural areas*58.9%23.0%43.8%24.9%58.9%54.5%41.8%65.5%61.8%Percentage of stillbirths born in health facilities*61.2%99.4%99.5%89.3%97.1%79.6%81.5%58.8%49.0%See web appendix for details and Blencowe et al for details of stillbirth rate estimates. *Based on urban/rural birth cohorts with national SBR so may underestimate rural SBR which is expected to higher than urban. For facility/home SBR differential, the direction of increased SBR is unpredictable as may be lower at home if high risk cases are in facilities, or higher at home if very low access to careFigure 3: Regional variation in stillbirth population-attributable risk for factors with adequate risk and appropriate prevalence data 9525093345Population Attributable Fraction %DemographicFetal conditionsNon-communicable conditionsInfectionsDemographicFetal conditionsNote that these factors are not mutually exclusive and some, particularly older age and non-communicable and lifestyle factors may coincideSee table 3 for conditions considered and Webappendix for more details Table 1: Top ten countries for absolute numbers of stillbirths, maternal and neonatal deaths in 2015CountryRank for stillbirth numbers in 2015 (2000) Number of stillbirths in 2015 Rank for numbers of neonatal deaths in 2015 Number of neonatal deaths in 2015 Rank for numbers of maternal deaths in 2015Number of maternal deaths in 2015GFR in 2015 (ARR:2000-15) (ARR:2000-15) (ARR:2000-15) (ARR:2000-15) India1 (1) 617,800(-2.2) 1703,600(-3.2)147,200(-4.4)0.08(-1.9)Nigeria2 (2) 341,800(-1.3) 2255,200(-2.3)239,100(-3.9)0.18(-0.3)Pakistan3 (3) 222,500(-1.2) 3209,200(-1.9)77,400(-3.7)0.09(-2.5)China4 (4) 131,300(-4.6) 499,500(-8.6)95,800(-4.4)0.05(0.5)Ethiopia5 (6) 99,200(-2.1) 687,800(-3.7)412,200(-6.1)0.13(-2.7)Democratic Republic of the Congo6 (8) 95,200(-1.0) 589,900(-1.7)320,300(-3.1)0.18(-1.2)Bangladesh7 (5) 89,900(-2.8) 772,300(-3.9)144,800(-5.2)0.07(-3.1)Indonesia8 (7) 65,200(-1.8) 862,200(-3.2)58,500(-3.4)0.07(-1.0)United Republic of Tanzania 9 (11) 41,400(-2.2) 1136,600(-3.5)67,600(-4.6)0.17(-0.6)Uganda10 (13) 38,500(-2.0) 1435,100(-2.7)105,700(-4.3)0.19(-1.2)Total?1.7 million stillbirths(65% world total)?1.7 million neonatal deaths(62% world total)?158,600 maternal deaths(58% world total)?See web appendix for details and Blencowe et al for details of stillbirth rate estimatesTable 2: Proportion of all stillbirths reported to be associated with congenital abnormalities in 18 national reports (2009-2013) and subnational in South Africa (2012-13) showing status of screening and legality of termination of pregnancyCountry(Year)Stillbirth definitionStillbirth rateCongenital cause-specific stillbirth ratePercentage of all stillbirths attributed to congenitalStatus of screening for congenital abnormalitiesLegal status of Termination of Pregnancy (TOP) for congenital abnormalitiesAustralia2011>=28 weeks2.90.310Widely availableLegal in most regionsColombia2013>=28 weeks80.78.3Availability <50%Legal (severe only)Kuwait2012>=28 weeks5.90.47.3Widely availableLegal Suriname2010-11>=28 weeks22.41.56.7Limited availabilityNot permittedArgentina2012>=1000g5.20.36Widely availableNot permittedPanama2013>=7 months50.47Limited availabilityNot permittedWales2013>=24 weeks4.20.37.1Widely availableLegalUK2009>=24 weeks5.20.47.4Widely availableLegalPortugal2012>=22 weeks3.60.38Widely availableLegalLithuania2013>=22 weeks4.80.59.7Widely availableLegalCosta Rica2013>=22 weeks6.80.46.4Widely availableLegalCanada2010>=500g3.80.411.4Widely availableLegalIreland2012>=500g3.90.821Widely availableNot permittedScotland2012>=500g4.70.511Widely availableLegalGuatemala*2013>=20 weeks8.60.55.4Limited availabilityNot permittedMexico*2012All fetal deaths8.70.67.3VariableNot permittedEcuador*2013All fetal deaths7.40.56.4Not knownNot permittedQatar*2009Not stated6.70.811.4Widely availableLegal (<5th Month)Subnational???????South Africa - non-tertiary hospitals**2012-13>=1000g140.42.5Very limited availabilityLegalSouth Africa - tertiary referral**2012-13>=1000g27.22.17.7Limited availabilityLegal* stillbirth ascertainment at <22 weeks likely low in these settings**Programme for identification of Perinatal Priorities (PIPP) covered 73% of all births nationally in these years See WebAppendix for full details of the sourcesTable 3: Conditions associated with stillbirth reviewed for risk factor analysisPotentially modifiable risk factorsPrevalence dataRisk dataCommentMATERNAL FACTORSDemographic / fertilityMaternal age >35√√?Maternal age <18XXData only available for girls aged 15 – 19 years old suggesting no increased risk but likely to be higher risk for younger age groupPrimiparityXX?Short inter-pregnancy interval XX?Assisted reproductive therapyXX?InfectionsSyphilis√√?HIV√√?Malaria√√?RubellaXX?VaricellaXX?ParvovirusXX?ToxoplasmosisXX?CMVXX?Tuberculosis√X?InfluenzaXX?HepatitisXX?ChorioamnionitisXX?Nutritional???Overweight √√?Obesity √√?Short maternal statureXX?Undernutrition√XNo studies showing convincing risk when confounding consideredMaternal anaemiaLimitedX1 study - no adjustment for potential confoundersNon-communicable diseases???Maternal diabetes (pre-existing)√√Adult females prevalence dataGestational DiabetesX√?Maternal hypertensive disorders:???Pre-existing√√Prevalence data based on adult female hypertensionPregnancy-inducedX√?Pre-eclampsia√√?Eclampsia√√?Untreated thyroid diseaseXX?Obstetric CholestasisXX?Maternal mental health disordersXXStudies report non-standard exposures, and close association with substance abuseMaternal HbSS√√?Lifestyle influencesTobacco√√Adult females prevalence dataAlcohol√XAdult females prevalence dataIllicit drug useX√?Violence against women√√?Environmental factors???Indoor air pollution√√?FETAL FACTORS??Male sex√√Not modifiable?Post-term pregnancy√√?Small for Gestational ageOnly for LMICsNAOn the causal pathway for many of the risk factorsCongenital abnormalitiesXNAConsidered as direct causeRhesus Disease√√?√ = data available X = no data available. LMIC=Low-Middle income countrySee WebAppendix for detail ................
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