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1.  A strategy for reducing maternal and newborn deaths by 2015 and beyond 
Background
Achievement of Millennium Development Goal (MDG) 4 for child survival requires acceleration of gains in newborn survival, and current trends in improving maternal health will also fall short of reaching MDG 5 without more strategic actions. We present a Maternal Newborn and Child Health (MNCH) strategy for accelerating progress on MDGs 4 and 5, sustaining the gains beyond 2015, and further bringing down maternal and child mortality by two thirds by 2030.
Discussion
The strategy takes into account current trends in coverage and cause-specific mortality, builds on lessons learned about what works in large-scale implementation programs, and charts a course to reach those who do not yet access services. A central hypothesis of this strategy is that enhancing interactions between frontline workers and mothers and families is critical for increasing the effective coverage of life-saving interventions. We describe a framework for measuring and evaluating progress which enables continuous course correction and improvement in program performance and impact.
Summary
Evidence for the hypothesis and impact of this strategy is being gathered and will be synthesized and disseminated in order to advance global learning and to maximise the potential to improve maternal and neonatal survival.
doi:10.1186/1471-2393-13-216
PMCID: PMC3866510  PMID: 24261785
2.  Levels, timing, and etiology of stillbirths in Sylhet district of Bangladesh 
Background
Lack of data is a critical barrier to addressing the problem of stillbirth in countries with the highest stillbirth burden. Our study objective was to estimate the levels, types, and causes of stillbirth in rural Sylhet district of Bangladesh.
Methods
A complete pregnancy history was taken from all women (n = 39 998) who had pregnancy outcomes during 2003-2005 in the study area. Verbal autopsy data were obtained for all identified stillbirths during the period. We used pre-defined case definitions and computer programs to assign causes of stillbirth for selected causes containing specific signs and symptoms. Both non-hierarchical and hierarchical approaches were used to assign causes of stillbirths.
Results
A total of 1748 stillbirths were recorded during 2003-2005 from 48,192 births (stillbirth rate: 36.3 per 1000 total births). About 60% and 40% of stillbirths were categorized as antepartum and intrapartum, respectively. Maternal conditions, including infections, hypertensive disorders, and anemia, contributed to about 29% of total antepartum stillbirths. About 50% of intrapartum stillbirths were attributed to obstetric complications. Maternal infections and hypertensive disorders contributed to another 11% of stillbirths. A cause could not be assigned in nearly half (49%) of stillbirths.
Conclusion
The stillbirth rate is high in rural Bangladesh. Based on algorithmic approaches using verbal autopsy data, a substantial portion of stillbirths is attributable to maternal conditions and obstetric complications. Programs need to deliver community-level interventions to prevent and manage maternal complications, and to develop strategies to improve access to emergency obstetric care. Improvements in care to avert stillbirth can be accomplished in the context of existing maternal and child health programs. Methodological improvements in the measurement of stillbirths, especially causes of stillbirths, are also needed to better define the burden of stillbirths in low-resource settings.
doi:10.1186/1471-2393-11-25
PMCID: PMC3088895  PMID: 21453544
3.  Delivering interventions to reduce the global burden of stillbirths: improving service supply and community demand 
BMC Pregnancy and Childbirth  2009;9(Suppl 1):S7.
Background
Although a number of antenatal and intrapartum interventions have shown some evidence of impact on stillbirth incidence, much confusion surrounds ideal strategies for delivering these interventions within health systems, particularly in low-/middle-income countries where 98% of the world's stillbirths occur. Improving the uptake of quality antenatal and intrapartum care is critical for evidence-based interventions to generate an impact at the population level. This concluding paper of a series of papers reviewing the evidence for stillbirth interventions examines the evidence for community and health systems approaches to improve uptake and quality of antenatal and intrapartum care, and synthesises programme and policy recommendations for how best to deliver evidence-based interventions at community and facility levels, across the continuum of care, to reduce stillbirths.
Methods
We systematically searched PubMed and the Cochrane Library for abstracts pertaining to community-based and health-systems strategies to increase uptake and quality of antenatal and intrapartum care services. We also sought abstracts which reported impact on stillbirths or perinatal mortality. Searches used multiple combinations of broad and specific search terms and prioritised rigorous randomised controlled trials and meta-analyses where available. Wherever eligible randomised controlled trials were identified after a Cochrane review had been published, we conducted new meta-analyses based on the original Cochrane criteria.
Results
In low-resource settings, cost, distance and the time needed to access care are major barriers for effective uptake of antenatal and particularly intrapartum services. A number of innovative strategies to surmount cost, distance, and time barriers to accessing care were identified and evaluated; of these, community financial incentives, loan/insurance schemes, and maternity waiting homes seem promising, but few studies have reported or evaluated the impact of the wide-scale implementation of these strategies on stillbirth rates. Strategies to improve quality of care by upgrading the skills of community cadres have shown demonstrable impact on perinatal mortality, particularly in conjunction with health systems strengthening and facilitation of referrals. Neonatal resuscitation training for physicians and other health workers shows potential to prevent many neonatal deaths currently misclassified as stillbirths. Perinatal audit systems, which aim to improve quality of care by identifying deficiencies in care, are a quality improvement measure that shows some evidence of benefit for changes in clinical practice that prevent stillbirths, and are strongly recommended wherever practical, whether as hospital case review or as confidential enquiry at district or national level.
Conclusion
Delivering interventions to reduce the global burden of stillbirths requires action at all levels of the health system. Packages of interventions should be tailored to local conditions, including local levels and causes of stillbirth, accessibility of care and health system resources and provider skill. Antenatal care can potentially serve as a platform to deliver interventions to improve maternal nutrition, promote behaviour change to reduce harmful exposures and risk of infections, screen for and treat risk factors, and encourage skilled attendance at birth. Following the example of high-income countries, improving intrapartum monitoring for fetal distress and access to Caesarean section in low-/middle-income countries appears to be key to reducing intrapartum stillbirth. In remote or low-resource settings, families and communities can be galvanised to demand and seek quality care through financial incentives and health promotion efforts of local cadres of health workers, though these interventions often require simultaneous health systems strengthening. Perinatal audit can aid in the development of better standards of care, improving quality in health systems. Effective strategies to prevent stillbirth are known; gaps remain in the data, the evidence and perhaps most significantly, the political will to implement these strategies at scale.
doi:10.1186/1471-2393-9-S1-S7
PMCID: PMC2679413  PMID: 19426470
4.  Reducing stillbirths: interventions during labour 
BMC Pregnancy and Childbirth  2009;9(Suppl 1):S6.
Background
Approximately one million stillbirths occur annually during labour; most of these stillbirths occur in low and middle-income countries and are associated with absent, inadequate, or delayed obstetric care. The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care, including prompt recognition and management of intrapartum complications. The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematically examined.
Methods
We undertook a systematic review of the published literature, searching PubMed and the Cochrane Library, of trials and reviews (N = 230) that reported stillbirth or perinatal mortality outcomes for eight interventions delivered during labour. Where eligible randomised controlled trials had been published after the most recent Cochrane review on any given intervention, we incorporated these new trial findings into a new meta-analysis with the Cochrane included studies.
Results
We found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality, especially on stillbirths. Available evidence suggests that operative delivery, especially Caesarean section, contributes to decreased stillbirth rates. Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact, though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour. Planned Caesarean section for term breech presentation has been shown in a large randomised trial to reduce stillbirths, but the feasibility and consequences of implementing this intervention routinely in low-/middle-income countries add caveats to recommending its use. Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures, but studies have not demonstrated impact on perinatal mortality. There was limited evidence of impact for maternal hyperoxygenation, and concerns remain about maternal safety. Transcervical amnioinfusion for meconium staining appears promising for low/middle income-country application according to the findings of many small studies, but a large randomised trial of the intervention had no significant impact on perinatal mortality, suggesting that further studies are needed.
Conclusion
Although the global appeal to prioritise access to emergency obstetric care, especially vacuum extraction and Caesarean section, rests largely on observational and population-based data, these interventions are clearly life-saving in many cases of fetal compromise. Safe, comprehensive essential and emergency obstetric care is particularly needed, and can make the greatest impact on stillbirth rates, in low-resource settings. Other advanced interventions such as amnioinfusion and hyperoxygenation may reduce perinatal mortality, but concerns about safety and effectiveness require further study before they can be routinely included in programs.
doi:10.1186/1471-2393-9-S1-S6
PMCID: PMC2679412  PMID: 19426469
5.  Reducing stillbirths: screening and monitoring during pregnancy and labour 
BMC Pregnancy and Childbirth  2009;9(Suppl 1):S5.
Background
Screening and monitoring in pregnancy are strategies used by healthcare providers to identify high-risk pregnancies so that they can provide more targeted and appropriate treatment and follow-up care, and to monitor fetal well-being in both low- and high-risk pregnancies. The use of many of these techniques is controversial and their ability to detect fetal compromise often unknown. Theoretically, appropriate management of maternal and fetal risk factors and complications that are detected in pregnancy and labour could prevent a large proportion of the world's 3.2 million estimated annual stillbirths, as well as minimise maternal and neonatal morbidity and mortality.
Methods
The fourth in a series of papers assessing the evidence base for prevention of stillbirths, this paper reviews available published evidence for the impact of 14 screening and monitoring interventions in pregnancy on stillbirth, including identification and management of high-risk pregnancies, advanced monitoring techniques, and monitoring of labour. Using broad and specific strategies to search PubMed and the Cochrane Library, we identified 221 relevant reviews and studies testing screening and monitoring interventions during the antenatal and intrapartum periods and reporting stillbirth or perinatal mortality as an outcome.
Results
We found a dearth of rigorous evidence of direct impact of any of these screening procedures and interventions on stillbirth incidence. Observational studies testing some interventions, including fetal movement monitoring and Doppler monitoring, showed some evidence of impact on stillbirths in selected high-risk populations, but require larger rigourous trials to confirm impact. Other interventions, such as amniotic fluid assessment for oligohydramnios, appear predictive of stillbirth risk, but studies are lacking which assess the impact on perinatal mortality of subsequent intervention based on test findings. Few rigorous studies of cardiotocography have reported stillbirth outcomes, but steep declines in stillbirth rates have been observed in high-income settings such as the U.S., where cardiotocography is used in conjunction with Caesarean section for fetal distress.
Conclusion
There are numerous research gaps and large, adequately controlled trials are still needed for most of the interventions we considered. The impact of monitoring interventions on stillbirth relies on use of effective and timely intervention should problems be detected. Numerous studies indicated that positive tests were associated with increased perinatal mortality, but while some tests had good sensitivity in detecting distress, false-positive rates were high for most tests, and questions remain about optimal timing, frequency, and implications of testing. Few studies included assessments of impact of subsequent intervention needed before recommending particular monitoring strategies as a means to decrease stillbirth incidence. In high-income countries such as the US, observational evidence suggests that widespread use of cardiotocography with Caesarean section for fetal distress has led to significant declines in stillbirth rates. Efforts to increase availability of Caesarean section in low-/middle-income countries should be coupled with intrapartum monitoring technologies where resources and provider skills permit.
doi:10.1186/1471-2393-9-S1-S5
PMCID: PMC2679411  PMID: 19426468
6.  Reducing stillbirths: prevention and management of medical disorders and infections during pregnancy 
BMC Pregnancy and Childbirth  2009;9(Suppl 1):S4.
Background
An estimated two-thirds of the world's 3.2 million stillbirths occur antenatally, prior to labour, and are often overlooked in policy and programs. Poorly recognised, untreated or inadequately treated maternal infections such as syphilis and malaria, and maternal conditions including hypertensive disorders, are known risk factors for stillbirth.
Methods
We undertook a systematic review of the evidence for 16 antenatal interventions with the potential to prevent stillbirths. We searched a range of sources including PubMed and the Cochrane Library. For interventions with prior Cochrane reviews, we conducted additional meta-analyses including eligible newer randomised controlled trials following the Cochrane protocol. We focused on interventions deliverable at the community level in low-/middle-income countries, where the burden of stillbirths is greatest.
Results
Few of the studies we included reported stillbirth as an outcome; most that did were underpowered to assess this outcome. While Cochrane reviews or meta-analyses were available for many interventions, few focused on stillbirth or perinatal mortality as outcomes, and evidence was frequently conflicting. Several interventions showed clear evidence of impact on stillbirths, including heparin therapy for certain maternal indications; syphilis screening and treatment; and insecticide-treated bed nets for prevention of malaria. Other interventions, such as management of obstetric intrahepatic cholestasis, maternal anti-helminthic treatment, and intermittent preventive treatment of malaria, showed promising impact on stillbirth rates but require confirmatory studies. Several interventions reduced known risk factors for stillbirth (e.g., anti-hypertensive drugs for chronic hypertension), yet failed to show statistically significant impact on stillbirth or perinatal mortality rates. Periodontal disease emerged as a clear risk factor for stillbirth but no interventions have reduced stillbirth rates.
Conclusion
Evidence for some newly recognised risk factors for stillbirth, including periodontal disease, suggests the need for large, appropriately designed randomised trials to test whether intervention can minimise these risks and prevent stillbirths. Existing evidence strongly supports infection control measures, including syphilis screening and treatment and malaria prophylaxis in endemic areas, for preventing antepartum stillbirths. These interventions should be incorporated into antenatal care programs based on attributable risks and burden of disease.
doi:10.1186/1471-2393-9-S1-S4
PMCID: PMC2679410  PMID: 19426467
7.  Reducing stillbirths: behavioural and nutritional interventions before and during pregnancy 
BMC Pregnancy and Childbirth  2009;9(Suppl 1):S3.
Background
The vast majority of global stillbirths occur in low- and middle-income countries, and in many settings, the majority of stillbirths occur antenatally, prior to the onset of labour. Poor nutritional status, lack of antenatal care and a number of behaviours increase women's risk of stillbirth in many resource-poor settings. Interventions to reduce these risks could reduce the resulting burden of stillbirths, but the evidence for the impact of such interventions has not yet been comprehensively evaluated.
Methods
This second paper of a systematic review of interventions that could plausibly impact stillbirth rates covers 12 different interventions relating to behavioural and socially mediated risk factors, including exposures to harmful practices and substances, antenatal care utilisation and quality, and maternal nutrition before and during pregnancy. The search strategy reviewed indexed medical journals on PubMed and the Cochrane Library. If any eligible randomised controlled trials were identified that were published after the most recent Cochrane review, they were added to generate new meta-analyses. Interventions covered in this paper have a focus on low- and middle-income countries, both because of the large burden of stillbirths and because of the high prevalence of risk factors including maternal malnutrition and harmful environmental exposures. The reviews and studies belonging to these interventions were graded and conclusions derived about the evidence of benefit of these interventions.
Results
From a programmatic perspective, none of the interventions achieved clear evidence of benefit. Evidence for some socially mediated risk factors were identified, such as exposure to indoor air pollution and birth spacing, but still require the development of appropriate interventions. There is a need for additional studies on culturally appropriate behavioural interventions and clinical trials to increase smoking cessation and reduce exposure to smokeless tobacco. Balanced protein-energy supplementation was associated with reduced stillbirth rates, but larger well-designed trials are required to confirm findings. Peri-conceptional folic acid supplementation significantly reduces neural tube defects, yet no significant associated reductions in stillbirth rates have been documented. Evidence for other nutritional interventions including multiple micronutrient and Vitamin A supplementation is weak, suggesting the need for further research to assess potential of nutritional interventions to reduce stillbirths.
Conclusion
Antenatal care is widely used in low- and middle-income countries, and provides a natural facility-based contact through which to provide or educate about many of the interventions we reviewed. The impact of broader socially mediated behaviors, such as fertility decision-making, access to antenatal care, and maternal diet and exposures like tobacco and indoor air pollution during pregnancy, are poorly understood, and further research and appropriate interventions are needed to test the association of these behaviours with stillbirth outcomes. For most nutritional interventions, larger randomised controlled trials are needed which report stillbirths disaggregated from composite perinatal mortality. Many antepartum stillbirths are potentially preventable in low- and middle-income countries, particularly through dietary and environmental improvement, and through improving the quality of antenatal care – particularly including diagnosis and management of high-risk pregnancies – that pregnant women receive.
doi:10.1186/1471-2393-9-S1-S3
PMCID: PMC2679409  PMID: 19426466
8.  3.2 million stillbirths: epidemiology and overview of the evidence review 
BMC Pregnancy and Childbirth  2009;9(Suppl 1):S2.
More than 3.2 million stillbirths occur globally each year, yet stillbirths are largely invisible in global data tracking, policy dialogue and programme implementation. This mismatch of burden to action is due to a number of factors that keep stillbirths hidden, notably a lack of data and a lack of consensus on priority interventions, but also to social taboos that reduce the visibility of stillbirths and the associated family mourning. Whilst there are estimates of the numbers of stillbirths, to date there has been no systematic global analysis of the causes of stillbirths. The multiple classifications systems in use are often complex and are primarily focused on high-income countries. We review available data and propose a programmatic classification that is feasible and comparable across settings. We undertook a comprehensive global review of available information on stillbirths in order to 1) identify studies that evaluated risk factors and interventions to reduce stillbirths, 2) evaluate the level of evidence for interventions, 3) place the available evidence for interventions in a health systems context to guide programme implementation, and 4) elucidate key implementation, monitoring, and research gaps. This first paper in the series outlines issues in stillbirth data availability and quality, the global epidemiology of stillbirths, and describes the methodology and framework used for the review of interventions and strategies.
doi:10.1186/1471-2393-9-S1-S2
PMCID: PMC2679408  PMID: 19426465

Results 1-8 (8)