Stanley A. Edlavitch

Oral misoprostol in preventing postpartum haemorrhage in resource-poor communities: a randomised controlled trial

BACKGROUND Postpartum haemorrhage is a major cause of maternal mortality in the developing world. Although effective methods for prevention and treatment of such haemorrhage exist--such as the uterotonic drug oxytocin--most are not feasible in resource-poor settings where many births occur at home. We aimed to investigate whether oral misoprostol, a potential alternative to oxytocin, could prevent postpartum haemorrhage in a community home-birth setting. METHODS In a placebo-controlled trial undertaken between September, 2002, and December, 2005, 1620 women in rural India were randomised to receive oral misoprostol (n=812) or placebo (n=808) after delivery. 25 auxiliary nurse midwives undertook the deliveries, administered the study drug, and measured blood loss. The primary outcome was the incidence of acute postpartum haemorrhage (defined as > or =500 mL bleeding) within 2 h of delivery. Analysis was by intention-to-treat. The trial was registered with the US clinical trials database (http://www. clinicaltrials.gov) as number NCT00097123. FINDINGS Oral misoprostol was associated with a significant reduction in the rate of acute postpartum haemorrhage (12.0% to 6.4%, p<0.0001; relative risk 0.53 [95% CI 0.39-0.74]) and acute severe postpartum haemorrhage (1.2% to 0.2%, p<0.0001; 0.20 [0.04-0.91]. One case of postpartum haemorrhage was prevented for every 18 women treated. Misoprostol was also associated with a decrease in mean postpartum blood loss (262.3 mL to 214.3 mL, p<0.0001). Postpartum haemorrhage rates fell over time in both groups but remained significantly higher in the placebo group. Women taking misoprostol had a higher rate of transitory symptoms of chills and fever than the control. INTERPRETATION Oral misoprostol was associated with significant decreases in the rate of acute postpartum haemorrhage and mean blood loss. The drugs low cost, ease of administration, stability, and a positive safety profile make it a good option in resource-poor settings.

Drape estimation vs. visual assessment for estimating postpartum hemorrhage

Objective: To compare (1) visual estimation of postpartum blood loss with estimation using a specifically designed blood collection drape and (2) the drape estimate with a measurement of blood loss by photospectrometry. Methods: A randomized controlled study was performed with 123 women delivered at the District Hospital, Belgaum, India. The women were randomized to visual or drape estimation of blood loss. A subsample of 10 drape estimates was compared with photospectrometry results. Results: The visual estimate of blood loss was 33% less than the drape estimate. The interclass correlation of the drape estimate to photospectrometry measurement was 0.92. Conclusion: Drape estimation of blood loss is more accurate than visual estimation and may have particular utility in the developing world. Prompt detection of postpartum hemorrhage may reduce maternal morbidity and mortality in low‐resource settings.

Side effects of oral misoprostol for the prevention of postpartum hemorrhage: Results of a community-based randomised controlled trial in rural India

Objective. To investigate the side effects of 600 μg oral misoprostol given for the mother and the newborn to prevent postpartum hemorrhage (PPH). Methods. One thousand six hundred twenty women delivering at home or subcentres in rural India were randomised to receive misoprostol or placebo in the third stage of labour. Women were evaluated for shivering, fever, nausea, vomiting and diarrhea at 2 and 24 h postpartum. Newborns were evaluated within 24 h for diarrhea, vomiting and fever. Symptoms were graded as absent, mild-to-moderate or severe. Results. Women who received misoprostol had a significantly greater incidence of shivering (52%vs. 17%, p < 0.001) and fever (4.2%vs. 1.1%, p < 0.001) at 2 h postpartum compared with women who received placebo. At 24 h, women in the misoprostol group experienced significantly more shivering (4.6%vs. 1.4%, p < 0.001) and fever (1.4%vs. 0.4%, p < 0.03). There were no differences in nausea, vomiting or diarrhea between the two groups. There were no differences in the incidence of vomiting, diarrhea or fever for newborns. Conclusions. Misoprostol is associated with a significant increase in postpartum maternal shivering and fever with no side effects for the newborn. Given its proven efficacy for the prevention of PPH, the benefits of misoprostol are greater than the associated risks.

Factors associated with acute postpartum hemorrhage in low-risk women delivering in rural India.

Postpartum hemorrhage (PPH), a major cause of maternal mortality and morbidity in low‐income countries, can occur unpredictably. This study examined the sociodemographic, clinical, and perinatal characteristics of low‐risk women who experienced PPH.

Consanguinity, prematurity, birth weight and pregnancy loss: a prospective cohort study at four primary health center areas of Karnataka, India.

Objective:To determine whether consanguinity adversely influences pregnancy outcome in South India, where consanguinity is a common means of family property retention.Study Design:Data were collected from a prospective cohort of 647 consenting women, consecutively registered for antenatal care between 14 and 18 weeks gestation, in Belgaum district, Karnataka in 2005. Three-generation pedigree charts were drawn for consanguineous participants. χ 2-Test and Students t-test were used to assess categorical and continuous data, respectively, using SPSS version 14. Multivariate logistic regression adjusted for confounding variables.Result:Overall, 24.1% of 601 women with singleton births and outcome data were consanguineous. Demographic characteristics between study groups were similar. Non-consanguineous couples had fewer stillbirths (2.6 vs 6.9% P=0.017; adjusted P=0.050), miscarriages (1.8 vs 4.1%, P=0.097; adjusted P=0.052) and lower incidence of birth weight <2500 g (21.8 vs 29.5%, P=0.071, adjusted P=0.044). Gestation <37 weeks was 6.2% in both the groups. Adjusted for consanguinity and other potential confounders, age <20 years was protective of stillbirth (P=0.01), pregnancy loss (P=0.023) and preterm birth (P=0.013), whereas smoking (P=0.015) and poverty (P=0.003) were associated with higher rates of low birth weight.Conclusion:Consanguinity significantly increases pregnancy loss and birth weight <2500 g.

Conducting International Collaborative Research in Developing Nations

International research partnerships bring together some of the best and the brightest in an effort to tackle global health problems. Such collaborations also pose complex challenges, such as maintaining ethical principles in the conduct of research in developing nations. In implementing a randomized clinical trial to reduce postpartum hemorrhage (PPH) during childbirth in rural India, U.S. and Indian collaborators addressed three such issues: the appropriateness of an ethical randomized controlled trial in the developing world, the inclusion of a placebo arm, and the relevance of informed consent in a semiliterate rural population.

Variation in the postpartum hemorrhage rate in a clinical trial of oral misoprostol

Objective. The main objective of this study was to identify factors associated with variation in the rate of acute postpartum hemorrhage (PPH), defined as blood loss ≥ 500 mL within 2 hours of delivery, observed in a randomized clinical trial of misoprostol for the prevention of PPH, conducted in rural India. Although the women in the misoprostol group had a significantly lower probability of having a PPH, we also noted a reduction in the rate of PPH in the placebo group over the course of the study. We hypothesized that this was due to the changing skills of the auxiliary nurse midwives (ANMs) over the course of the study. Methods. We conducted a post-hoc analysis examining variation in PPH rates over the duration of the trial among the women randomized to the placebo arm (n = 808). Descriptive, correlation analysis and generalized estimating equations (GEE) were used to predict PPH rates. With no direct measure of ANM skills, we used proxy measures, including: (1) the ANMs point of entry into the study (original ANMs at the initiation of the trial were less skilled than replacement ANMs); (2) the study duration, representing exposure of the ANM to ongoing training and monitoring; and (3) duration of the second stage of labor as a measure of improved delivery practices. Results. As the study duration increased, the duration of the second stage of labor decreased (−0.12, p = 0.001) and as the duration of the second stage of labor decreased, the rate of PPH decreased (0.0282; 95% CI 0.0201–0.0363). For each 10-minute increase in the duration of second stage labor increased PPH odds by 7.1% and each 30-day duration of the trial decreased PPH odds by 3.4%. Additionally, a patient delivered by an original ANM was 3.14 times more likely to have a PPH compared to a patient delivered by a replacement ANM. Conclusions. Declining PPH rates were associated with improved skills and delivery practices that decreased duration of the second stage of labor. These improvements appeared to be consistent with the introduction of the more skilled replacement ANMs as well as ongoing training and monitoring for all ANMs over the duration of the trial.

Towards large-scale sharing of electronic health records of cancer patients

The rising cost of healthcare is one of the major concerns faced by the nation. One way to lower healthcare costs and provide better quality care to patients is through the effective use of Information Technology (IT). Data sharing and collaboration and large-scale management of healthcare data have been identified as important IT challenges to advance the nations healthcare system. In this paper, we present an overview of the software framework called CDN (Collaborative Data Network) that we are developing for large-scale sharing of electronic health records (EHR). In this on-going effort, we focus on sharing EHRs of cancer patients. Cancer is the second leading cause of deaths in the US. CDN is based on the synergistic combination of peer-to-peer technology and the extensible markup language XML and XQuery. We outline the key challenges that arise when sharing evolving, heterogeneous repositories and processing queries across multiple repositories. We present the novel architecture of CDN to overcome these challenges and discuss our plan for implementation, evaluation, and deployment.

Publishing negative findings and the challenge of avoiding type II errors in studies of suspect teratogens: Example of a recent ondansetron publication

It is important that negative, as well as positive, studies be published to complete the available picture in areas of scientific inquiry. At the same time, it is critical that the implications of a negative study not be overstated and generalized when major issues of study design and data accuracy may be the reason that no relationship was discovered. The challenge of avoiding type II errors in interpreting negative findings has major public health implications, especially when the relationship of an exposure to birth defects is the concern. This is particularly important when interpreting the report by Fazio et al. (June issue of Reproductive Toxicology) on the relationship of ondansetron exposure to pregnancy outcome and birth defects. This review addresses the study design and conclusions and suggests that an alternative concluding statement would be more apropos, given the limitations of the data.

Primary Prevention Research in Suicide

At the American Association of Suicidology’s (AAS) 46th Annual Conference in Austin, Texas (http://www.suicidology.org/web/guest/education-and-training/annualconference), participants were challenged to address why there has not been more progress in reducing the rates of completed suicides (Berman, 2013). A draft of recommendations from the National Action Alliance for Suicide Prevention’s Research Prioritization Task Force was presented at the meeting and subsequently published in this journal (National Action Alliance for Suicide Prevention [NAASP], 2013a, 2013b). The purpose of this commentary is to address this challenge by emphasizing the importance of employing a disease etiology strategy that integrates molecular data with clinical data, environmental data, and health outcomes in a dynamic, iterative fashion. The recommendations of the Research Prioritization Task Force tackle important public health program issues and are embedded within seven key questions, summarized as: 1. Why do people become suicidal? 2. How do we better detect/predict risk? 3. What interventions prevent suicidal behavior? 4. What are the effective services for treating suicidal persons and preventing suicidal behavior? 5. How do we reduce stigma? 6. What are the suicide prevention interventions outside of health-care settings? 7. Which existing and new infrastructure needs are required to further reduce suicidal behavior? (NAASP, 2013b; Silverman et al., 2013)