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. 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.

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.

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.

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.

Attitudes towards genetic diagnosis in Pakistan: a survey of medical and legal communities and parents of thalassemic children.

OBJECTIVES: It was the aim of this study to assess the attitudes of doctors, medical students, lawyers, parliament members and parents of thalassemic children towards genetic diagnosis in Pakistan. STUDY DESIGN: A cross-sectional descriptive survey was conducted among representative samples. RESULTS: Five hundred and seventy doctors, 49 lawyers, 178 medical students, 89 parents of thalassemic children and 16 members of parliament (MPs) were included in the survey. The groups showed considerable difference in their attitudes towards different aspects of the issue. A large proportion (88.5%) agreed to the idea of genetic diagnostic screening, especially the parents of thalassemic patients. Premarital carrier screening was favored by 77% of the respondents. Prenatal screening was most favored by the parents of thalassemic children (94.4%). Likewise, a majority of parents of thalassemic children were in favor of abortion in case of an affected fetus. Genetic self-screening was also favored most by the parents of thalassemic patients (78.2%). Only 24% of the doctors favored making genetic screening mandatory, whereas 63% of the parents agreed to the idea. CONCLUSION: Attitudes regarding genetic diagnosis are markedly different among various societal groups in Pakistan. The parents of the affected children strongly favor genetic screening as does the medical community, though not as strongly as the parents. The legislative groups, particularly the MPs, are reserved in their support. Genetic diagnosis can help decrease the disease burden in the future. However, it raises a number of ethical issues, which need to be addressed. It is important to educate the population about potential benefits as well as ethical dilemmas involved so that the general public is able to make the right decisions for themselves and their families.