Stillbirth in developing countries.

OBJECTIVE: To conduct a systematic review of the literature on stillbirths in developing countries. METHOD: Review of the English literature for all articles related to stillbirth in developing countries published from 1975 to 2005. RESULTS: Because almost half of the deliveries in developing countries occur at home, under-reporting of stillbirths is a huge problem, and reliable data about rates and causes are difficult to obtain. Hospital stillbirth data are often subject to substantial bias and the ability to generalize from these data is unknown. Nevertheless, at least 4 million stillbirths occur yearly, the vast majority in developing countries, with rates in many developing countries ten-fold higher than elsewhere. Prolonged and obstructed labor, preeclampsia and various infections, all without adequate treatment, account for the majority of stillbirths. CONCLUSION: Despite the large number of stillbirths worldwide, the topic of stillbirths in developing countries has received very little research, programmatic or policy attention. Better access to appropriate obstetric care, especially during labor, should reduce developing country stillbirth rates dramatically.     

Reducing stillbirths: prevention and management of medical disorders and infections during pregnancy

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.

     

Commentary: reducing the world's stillbirths

One of the major success stories of modern obstetrics in high-income countries in the last 5 decades is the reduction of stillbirths from rates as high as 50 per 1000 births to about 5 per 1000 births today. Fetal mortality associated with obstructed labour, asphyxia, hypertension, diabetes, Rh disease, placental abruption, post-term pregnancies and infections such as syphilis all have declined. Much of this success has occurred in term births in the intrapartum period so that most stillbirths in high-income countries now occur in the antepartum period and are pre-term. Current stillbirth rates in many low- and middle-income countries, and especially in those areas within the countries with poorly functioning health systems, approximate those seen in high-income countries 50 years ago. A major difference between the stillbirths occurring in high-income countries and those occurring elsewhere is the preponderance of late pre-term, term and intrapartum stillbirths in low-resource countries. Those stillbirths should be relatively easy to prevent by known risk assessment methods and prompt delivery, often by Cesarean section. This commentary addresses an extensive six-paper review of stillbirths with an emphasis on low- and middle-income countries. Among the conclusions are that while a number of interventions have been shown to be effective in reducing stillbirths, unless there is a functioning health system in which these interventions can be implemented, the potential for a sustainable and substantial reduction in stillbirth rates will not be reached.     

Reducing stillbirths: interventions during labour

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.

     

Reducing stillbirths: behavioural and nutritional interventions before and during pregnancy

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 in these countries. 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.

     

An assessment of stillbirths in a tertiary hospital in northern Nigeria

Objective: This study was undertaken to determine the stillbirth rate and causes in Birnin Kudu, North-west, Nigeria.

Method: This was a retrospective study. It involved 705 women who presented for delivery in Federal Medical Centre, Birnin Kudu and had stillbirths. The hospital maternity and theatre registers were used to identify the women who had stillbirth during the study period from 1 January 2008 to 31 December 2012. The data obtained were analyzed using SPSS version 16.0 statistical software. Significant association between socio-demographic/obstetrics factors and stillbirth were tested using the chi-square test and p?Result: The stillbirth rate was 170 per 1000 births. Most of the women who had stillbirths (29.1%) were aged 20–24 years, followed by those aged ≥35 years (27.1%). The uneducated women were more than those who had only primary education and this was statistically significant (p?=?0.001). The mean parity of the women was 5?±?3. Obstructed labour was the common cause of stillbirth followed by placental abruption (17.73%) and pre-eclampsia/eclampsia (13.33%).

Conclusion: The stillbirth rate reported in this study was higher than those reported from other regions of Nigeria and obstructed labour was the common cause.     

Trends and determinants of stillbirth in developing countries: results from the Global Network’s Population-Based Birth Registry

Background

Stillbirth rates remain high, especially in low and middle-income countries, where rates are 25 per 1000, ten-fold higher than in high-income countries. The United Nations’ Every Newborn Action Plan has set a goal of 12 stillbirths per 1000 births by 2030 for all countries.

Methods

From a population-based pregnancy outcome registry, including data from 2010 to 2016 from two sites each in Africa (Zambia and Kenya) and India (Nagpur and Belagavi), as well as sites in Pakistan and Guatemala, we evaluated the stillbirth rates and rates of annual decline as well as risk factors for 427,111 births of which 12,181 were stillbirths.

Results

The mean stillbirth rates for the sites were 21.3 per 1000 births for Africa, 25.3 per 1000 births for India, 56.9 per 1000 births for Pakistan and 19.9 per 1000 births for Guatemala. From 2010 to 2016, across all sites, the mean stillbirth rate declined from 31.7 per 1000 births to 26.4 per 1000 births for an average annual decline of 3.0%. Risk factors for stillbirth were similar across the sites and included maternal age < 20 years and age > 35 years. Compared to parity 1–2, zero parity and parity > 3 were both associated with increased stillbirth risk and compared to women with any prenatal care, women with no prenatal care had significantly increased risk of stillbirth in all sites.

Conclusions

At the current rates of decline, stillbirth rates in these sites will not reach the Every Newborn Action Plan goal of 12 per 1000 births by 2030. More attention to the risk factors and treating the causes of stillbirths will be required to reach the Every Newborn Action Plan goal of stillbirth reduction.

Trial registration

NCT01073475.

     

Challenges in classification and assignment of causes of stillbirths in low- and lower middle-income countries

Stillbirths account for 2.6 million deaths annually. 98% occur in low- and lower middle-income countries. Accurate classification of stillbirths in low-resource settings is challenged by poor pregnancy dating and infrequent access to electronic heart rate monitoring for both the newborn and fetus. In these settings, liveborn infants may be misclassified as stillbirths, and stillbirths may be misclassified as miscarriages. Causation is available for only 3% of stillbirths globally due to the absence of registration systems. In low-resource settings where culture and autopsy are infrequently available, clinical course is used to assign cause of stillbirth. This method may miss rare or subtle causes, as well as those with non-specific clinical presentations. Verbal autopsy is another technique for assigning cause of stillbirth when objective medical data are limited. This method requires family engagement and physician attribution of cause. As interventions to reduce stillbirths in LMICs are increasingly implemented, attention to accurate classification and assignment of causes of stillbirth are critical to charting progress.     

Maternal mortality, stillbirth and measures of obstetric care in developing and developed countries.

OBJECTIVE: Maternal mortality and stillbirths are important adverse pregnancy outcomes, especially in developing countries. Because underlying causes of both outcomes appeared similar, the relationship between maternal mortality, stillbirth and three measures of obstetrical care were studied. METHODS: Using data provided by the World Health Organization from 188 developed and developing countries, correlations and linear regression analyses between maternal mortality and stillbirth rates and cesarean section rates, skilled delivery attendance, and >or=4 prenatal visits) were developed. RESULTS: Stillbirth and maternal mortality rates were strongly correlated, with about 5 stillbirths for each maternal death. However, the ratio increased from about 2 to 1 in least developed countries to 50 to 1 in the most developed countries. In developing countries, as the cesarean section rates increased from 0 to about 10%, both maternal mortality and stillbirth rates decreased sharply. Skilled delivery attendance was not associated with significant reductions in maternal mortality or stillbirth rates until coverage rates of about 40% were achieved. Four or more antenatal visits were not associated with significant reductions in maternal deaths until about 60% coverage was achieved. The same measure was associated with only modest decreases in stillbirth. CONCLUSION: Across countries, stillbirth was significantly associated with maternal mortality. Both stillbirth and maternal mortality were similarly related to all three measures of obstetric care. An increase in cesarean section rates from 0 to 10% was associated with sharp decreases in both maternal mortality and stillbirths.     

Count every newborn: EN-BIRTH study improving facility-based coverage and quality measurement in routine information systems

Background

An estimated >2 million babies stillborn around the world each year lack visibility. Low- and middle-income countries carry 84% of the burden yet have the least data. Most births are now in facilities, hence routine register-recording presents an opportunity to improve counting of stillbirths, but research is limited, particularly regarding accuracy. This paper evaluates register-recorded measurement of hospital stillbirths, classification accuracy, and barriers and enablers to routine recording.

Methods

The EN-BIRTH mixed-methods, observational study took place in five hospitals in Bangladesh, Nepal and Tanzania (2017–2018). Clinical observers collected time-stamped data on perinatal care and birth outcomes as gold standard. To assess accuracy of routine register-recorded stillbirth rates, we compared birth outcomes recorded in labour ward registers to observation data. We calculated absolute rate differences and individual-level validation metrics (sensitivity, specificity, percent agreement). We assessed misclassification of stillbirths with neonatal deaths. To examine stillbirth appearance (fresh/macerated) as a proxy for timing of death, we compared appearance to observed timing of intrauterine death based on heart rate at admission.

Results

23,072 births were observed including 550 stillbirths. Register-recorded completeness of birth outcomes was > 90%. The observed study stillbirth rate ranged from 3.8 (95%CI = 2.0,7.0) to 50.3 (95%CI = 43.6,58.0)/1000 total births and was under-estimated in routine registers by 1.1 to 7.3 /1000 total births (register: observed ratio 0.9–0.7). Specificity of register-recorded birth outcomes was > 99% and sensitivity varied between hospitals, ranging from 77.7–86.1%. Percent agreement between observer-assessed birth outcome and register-recorded birth outcome was very high across all hospitals and all modes of birth (> 98%). Fresh or macerated stillbirth appearance was a poor proxy for timing of stillbirth. While there were similar numbers of stillbirths misclassified as neonatal deaths (17/430) and neonatal deaths misclassified as stillbirths (21/36), neonatal deaths were proportionately more likely to be misclassified as stillbirths (58.3% vs 4.0%). Enablers to more accurate register-recording of birth outcome included supervision and data use.

Conclusions

Our results show these routine registers accurately recorded stillbirths. Fresh/macerated appearance was a poor proxy for intrapartum stillbirths, hence more focus on measuring fetal heart rate is crucial to classification and importantly reduction in these preventable deaths.

     

Etiology of stillbirth at term: a 10-year cohort study

Objective. To examine etiological factors contributing to cases of intrauterine fetal demise in term pregnancies over a 10-year period.

Methods. This was a retrospective cohort analysis of 29 908 term (37⁺⁰ to 41⁺⁶ weeks gestation) infants delivering in a single tertiary-referral university institution over the 10-year period from 1996 to 2005. Cases of stillbirth were identified from a computerized hospital database, and pathological, clinical, and biochemical data were reviewed for all cases. Trends were analyzed using the Cusick test for trend. Categorical data were analyzed using the Fisher's exact test, with the 5% level considered significant.

Results. The incidence of intrauterine fetal demise at term was 1.8 per 1000 at-risk pregnancies. There was no significant downward trend in the rate of term stillbirth between 1996 and 2005 (p = 0.0808). Stillbirths were unexplained in 51% of cases, although in many cases a possible etiological factor was identified but not necessarily proven. There was a significant downward trend in the incidence of unexplained term stillbirths at our institution over the 10-year study period (p = 0.0105). Placental/cord factors accounted for 25% of term stillbirths and did not decrease significantly over the study period (p = 0.0953). Almost 50% of term stillbirths occurred in women who registered late or had no antenatal care. However, suboptimal antenatal care was not predictive of differences in either acceptance of perinatal postmortem or successful identification of stillbirth etiology.

Conclusions. The incidence of stillbirth at term is 2 per 1000 term pregnancies and has not changed significantly in the past 10 years. Almost 50% of term stillbirths occurred in women with suboptimal antenatal care. More than half of cases are unexplained, often resulting from an incomplete diagnostic work-up. Despite this, there has been a significant downward trend in the rates of unexplained stillbirth at term. It is imperative that a complete diagnostic work-up is performed in cases of term stillbirth, to minimize the incidence of unexplained stillbirth.     

First-trimester metabolomic prediction of stillbirth

Background: Stillbirth remains a major problem in both developing and developed countries. Omics evaluation of stillbirth has been highlighted as a top research priority.

Objective: To identify new putative first-trimester biomarkers in maternal serum for stillbirth prediction using metabolomics-based approach.

Methods: Targeted, nuclear magnetic resonance (NMR) and mass spectrometry (MS), and untargeted liquid chromatography-MS (LC-MS) metabolomic analyses were performed on first-trimester maternal serum obtained from 60 cases that subsequently had a stillbirth and 120 matched controls. Metabolites by themselves or in combination with clinical factors were used to develop logistic regression models for stillbirth prediction. Prediction of stillbirths overall, early (<28 weeks and <32 weeks), those related to growth restriction/placental disorder, and unexplained stillbirths were evaluated.

Results: Targeted metabolites including glycine, acetic acid, L-carnitine, creatine, lysoPCaC18:1, PCaeC34:3, and PCaeC44:4 predicted stillbirth overall with an area under the curve [AUC, 95% confidence interval (CI)]?=?0.707 (0.628–0.785). When combined with clinical predictors the AUC value increased to 0.740 (0.667–0.812). First-trimester targeted metabolites also significantly predicted early, unexplained, and placental-related stillbirths. Untargeted LC-MS features combined with other clinical predictors achieved an AUC (95%CI)?=?0.860 (0.793–0.927) for the prediction of stillbirths overall. We found novel preliminary evidence that, verruculotoxin, a toxin produced by common household molds, might be linked to stillbirth.

Conclusions: We have identified novel biomarkers for stillbirth using metabolomics and demonstrated the feasibility of first-trimester prediction.     

The project to understand and research preterm pregnancy outcomes and stillbirths in South Asia (PURPOSe): a protocol of a prospective,cohort study of causes of mortality among preterm births and stillbirths

Background

In South Asia, where most stillbirths and neonatal deaths occur, much remains unknown about the causes of these deaths. About one-third of neonatal deaths are attributed to prematurity, yet the specific conditions which cause these deaths are often unclear as is the etiology of stillbirths. In low-resource settings, most women are not routinely tested for infections and autopsy is rare.

Methods

This prospective, cohort study will be conducted in hospitals in Davengere, India and Karachi, Pakistan. All women who deliver either a stillbirth or a preterm birth at one of the hospitals will be eligible for enrollment. With consent, the participant and, when applicable, her offspring, will be followed to 28-days post-delivery. A series of research tests will be conducted to determine infection and presence of other conditions which may contribute to the death. In addition, all routine clinical investigations will be documented. For both stillbirths and preterm neonates who die ≤ 28 days, with consent, a standard autopsy as well as minimally invasive tissue sampling will be conducted. Finally, an expert panel will review all available data for stillbirths and neonatal deaths to determine the primary and contributing causes of death using pre-specified guidance.

Conclusion

This will be among the first studies to prospectively obtain detailed information on causes of stillbirth and preterm neonatal death in low-resource settings in Asia. Determining the primary causes of death will be important to inform strategies most likely to reduce the high mortality rates in South Asia.

Trial registration

Clinicaltrials.gov (NCT03438110) Clinical Trial Registry of India (CTRI/2018/03/012281).

     

Delivering interventions to reduce the global burden of stillbirths: improving service supply and community demand

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.

     

Stillbirths: epidemiology, evidence, and priorities for action

The annual global burden of stillbirths amounts to an estimated 3.2 million%, 98% of which occur in low- and middle-income countries (LMICs). Of these, 1.02 million (32%) are intrapartum, ie, taking place during labor. The most important causes of stillbirths in LMICs include obstructed or prolonged labor, hypertensive diseases of pregnancy, syphilis and gram-negative infections, malaria in endemic areas, and undernutrition. Interventions that target these causes can play an important role in reducing stillbirths. There is a clear benefit of emergency obstetrical care, particularly Cesarean delivery, on intrapartum rates in LMICs when Cesarean rates are less than 8% to 10%. Provision of a skilled birth attendant is another important intervention whereby labor complications can be prevented, identified, managed, and/or referred. Among interventions for infections, syphilis screening and treatment can prevent as many as 50% of all stillbirths in areas with high syphilis prevalence, reducing the risk of stillbirths among treated women to that of untreated women. Intermittent preventive treatment of malaria and insecticide-treated mosquito nets are also interventions with strong recommendation, especially in the first 2 pregnancies. Balanced energy protein supplementation is an important nutritional intervention to prevent stillbirths in undernourished women, especially in LMICs. Creation of increased demand for health services within communities and increasing their uptake also can play a role in averting stillbirths. Other potential social and behavioral interventions include birth spacing, smoking cessation and indoor air pollution control, although the evidence for these is weak.     

Global report on preterm birth and stillbirth (2 of 7): discovery science

Background

Normal and abnormal processes of pregnancy and childbirth are poorly understood. This second article in a global report explains what is known about the etiologies of preterm births and stillbirths and identifies critical gaps in knowledge. Two important concepts emerge: the continuum of pregnancy, beginning at implantation and ending with uterine involution following birth; and the multifactorial etiologies of preterm birth and stillbirth. Improved tools and data will enable discovery scientists to identify causal pathways and cost-effective interventions.

Pregnancy and parturition continuum

The biological process of pregnancy and childbirth begins with implantation and, after birth, ends with the return of the uterus to its previous state. The majority of pregnancy is characterized by rapid uterine and fetal growth without contractions. Yet most research has addressed only uterine stimulation (labor) that accounts for <0.5% of pregnancy.

Etiologies

The etiologies of preterm birth and stillbirth differ by gestational age, genetics, and environmental factors. Approximately 30% of all preterm births are indicated for either maternal or fetal complications, such as maternal illness or fetal growth restriction. Commonly recognized pathways leading to preterm birth occur most often during the gestational ages indicated: (1) inflammation caused by infection (22-32 weeks); (2) decidual hemorrhage caused by uteroplacental thrombosis (early or late preterm birth); (3) stress (32-36 weeks); and (4) uterine overdistention, often caused by multiple fetuses (32-36 weeks). Other contributors include cervical insufficiency, smoking, and systemic infections. Many stillbirths have similar causes and mechanisms. About two-thirds of late fetal deaths occur during the antepartum period; the other third occur during childbirth. Intrapartum asphyxia is a leading cause of stillbirths in low- and middle-income countries.

Recommendations

Utilizing new systems biology tools, opportunities now exist for researchers to investigate various pathways important to normal and abnormal pregnancies. Improved access to quality data and biological specimens are critical to advancing discovery science. Phenotypes, standardized definitions, and uniform criteria for assessing preterm birth and stillbirth outcomes are other immediate research needs.

Conclusion

Preterm birth and stillbirth have multifactorial etiologies. More resources must be directed toward accelerating our understanding of these complex processes, and identifying upstream and cost-effective solutions that will improve these pregnancy outcomes.

     

Reducing stillbirths: screening and monitoring during pregnancy and labour

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.

     

The influence of obstetric intervention on trends in twin stillbirths: United States, 1989–99

Objective: Although twin stillbirth rates have declined substantially over the past two decades, the contribution of changes in obstetric interventions to reducing twin stillbirths has not been quantified.

Methods: We carried out a retrospective cohort study of twin live births and stillbirths in the United States between 1989 and 1999 (n?=?1?102?212). Changes in the rate of stillbirth (???22 weeks) before and after adjustment for changes in labor induction, Cesarean delivery and sociodemographic factors were estimated through ecological logistic regression analysis. This analysis was based on aggregating data by each state within the United States.

Results: Between 1989 and 1999, rates of labor induction and Cesarean delivery among twin live births increased by 138% (from 5.8% to 13.8%) and 15% (from 48.3% to 55.6%), respectively. These changes were accompanied by a 43% decline in the stillbirth rate between 1989 and 1999 (from 24.4 to 13.9 per 1000 fetuses at risk). After excluding births weighing <?500?g, rates of labor induction among twins at 22–27 weeks', 28–33 weeks' and ??34 weeks' gestation increased by 95%, 131% and 127%, respectively, between 1989 and 1999. Cesarean delivery rates also increased by 55%, 29% and 2% in these same gestational age categories. The 48% (relative risk (RR) 0.52, 95% confidence interval (CI) 0.49–0.55) decline in stillbirth rate between 1989–91 and 1997–99 was reduced to a 25% (RR 0.75, 95% CI 0.72–0.79) decline after adjustment for changes in labor induction and Cesarean delivery. The decline in the rate of twin stillbirths was larger at later gestational ages (at ??32 and ??34 weeks) where the largest absolute increases in labor induction rates were observed.

Conclusions: The use of Cesarean delivery and especially labor induction for twin pregnancies has increased substantially in the United States over the last decade and these changes have been associated with a large decline in the rate of stillbirth among twins.