NESTROFT-A Cost-Effective Mass Screening Tool for the Detection of ß-Thalassemia Carrier Status in Anemic Pregnant Women: A Step Toward Reducing the National Disease Burden.

Introduction ß-Thalassemias are inherited hemoglobinopathies commonly encountered in practice. With chances of a promising cure being rare, the prevention of births with this disorder should assume priority, especially in low-resource countries. This can be achieved by the implementation of a mass screening program that is reliable and, at the same time, cost-effective. Objectives This study focuses on the utility of Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT) as a mass screening tool to detect thalassemia carriers. Hematological parameters that may predict carrier status were also evaluated. Materials and Methods Hemoglobin estimation was performed on all consented pregnant women. If the patient was found to have hemoglobin < 11 g/dL, the blood sample was subjected to other routine hematological tests along with peripheral smear examination. NESTROFT was performed using 0.36% saline solution. Confirmation was done using high-performance liquid chromatography (HPLC). Statistical Analysis Data obtained were tabulated using version 21 of the Statistical Package for Social Sciences. Means, standard deviations, and percentages were used to describe the sample. Chi-square test and Students' t test were used to identify differences between the groups. Results Of 441 pregnant women enrolled, 206 were found to be anemic. Nineteen (9.2%) of the anemic pregnant women were detected to be carriers of hemoglobinopathies. Among the hematological parameters, mean red blood cell count and reticulocyte count were higher, while mean corpuscular hemoglobin concentration was lower in carriers. Also, carriers were more likely to present with microcytic hypochromic anemia. NESTROFT showed a sensitivity of 84.21%, specificity of 96.25%, a positive predictive value of 69.56%, and a negative predictive value of 98.36%. A false-positive result was seen in 3.74% of the tests, while a false negative result was seen in 15.78% of the tests. Conclusions NESTROFT (0.36%) can be used as a simple and cost-effective mass screening tool for the detection of carrier status. This should be followed by confirmation using HPLC or hemoglobin electrophoresis.

Incidence and characteristics of pregnancy-related death across ten low- and middle-income geographical regions: secondary analysis of a cluster randomised controlled trial.

OBJECTIVE: The aim of this article is to describe the incidence and characteristics of pregnancy-related death in low- and middle-resource settings, in relation to the availability of key obstetric resources. DESIGN: This is a secondary analysis of a stepped-wedge cluster randomised controlled trial. SETTING: This trial was undertaken at ten sites across eight low- and middle-income countries in sub-Saharan Africa, India and Haiti. POPULATION: Institutional-level consent was obtained and all women presenting for maternity care were eligible for inclusion. METHODS: Pregnancy-related deaths were collected prospectively from routine data sources and active case searching. MAIN OUTCOME MEASURES: Pregnancy-related death, place, timing and age of maternal death, and neonatal outcomes in women with this outcome. RESULTS: Over 20 months, in 536 233 deliveries there were 998 maternal deaths (18.6/10 000, range 28/10 000-630/10 000). The leading causes of death were obstetric haemorrhage (36.0%, n = 359), hypertensive disorders of pregnancy (20.6%, n = 206), sepsis (14.1%, n = 141) and other (26.5%, n = 264). Approximately a quarter of deaths occurred prior to delivery (28.4%, n = 283), 35.7% (n = 356) occurred on the day of delivery and 35.9% (n = 359) occurred after delivery. Half of maternal deaths (50.6%; n = 505) occurred in women aged 20-29 years, 10.3% (n = 103) occurred in women aged under 20 years, 34.5% (n = 344) occurred in women aged 30-39 years and 4.6% (n = 46) occurred in women aged ≥40 years. There was no measured association between the availability of key obstetric resources and the rate of pregnancy-related death. CONCLUSIONS: The large variation in the rate of pregnancy-related death, irrespective of resource availability, emphasises that inequality and inequity in health care persists. TWEETABLE ABSTRACT: Inequality and inequity in pregnancy-related death persists globally, irrespective of resource availability.

Clindamycin to reduce preterm birth in a low resource setting: a randomised placebo-controlled clinical trial.

OBJECTIVE: To determine whether oral clindamycin reduces the risk of preterm birth (PTB) in women with abnormal vaginal microflora as evidenced by a vaginal pH ≥5.0. DESIGN: Randomised double-blind placebo-controlled trial. SETTING: Rural southern India. POPULATION: Pregnant women with a singleton fetus between 13+0/7 weeks and 20+6/7 weeks. METHODS: Pregnant women were recruited during prenatal visits in Karnataka, India, from October 2013 to July 2015. Women were required to have a singleton fetus between 13+0/7 weeks and 20+6/7 weeks and an elevated vaginal pH (≥5.0) by colorimetric assessment. Participants were randomised to either oral clindamycin 300 mg twice daily for 5 days or an identical-appearing placebo. MAIN OUTCOME MEASURES: The primary outcome was the incidence of PTB, defined as delivery before 37+0/7 weeks. RESULTS: Of the 6476 screened women, 1727 women were randomised (block randomised in groups of six; clindamycin n = 866, placebo n = 861). The demographic, reproductive, and anthropomorphometric characteristics of the study groups were similar. Compliance was high, with over 94% of capsules being taken. The rate of PTB before 37 weeks was comparable between the two groups [clindamycin 115/826 (13.9%) versus placebo 111/806 (13.8%), between-group difference 0.2% (95% CI -3.2 to 3.5%, P = 0.93)], as was PTB at less than 34 weeks [clindamycin 40/826 (4.8%) versus placebo group 37/806 (4.6%), between-group difference 0.3% (95% CI -1.8 to 2.3%, P = 0.81)]. No differences were detected in the incidence of birthweight of<2500 g, <1500 g, miscarriage, stillbirth or neonatal death. CONCLUSION: In this setting, oral clindamycin did not decrease PTB among women with vaginal pH ≥5.0. TWEETABLE ABSTRACT: Oral clindamycin between 13+0/7 and 20+6/7 weeks does not prevent preterm birth in women with a vaginal pH ≥5.0.

Misoprostol for primary versus secondary prevention of postpartum haemorrhage: a cluster-randomised non-inferiority community trial.

OBJECTIVE: To assess whether secondary prevention, which preemptively treats women with above-average postpartum bleeding, is non-inferior to universal prophylaxis. DESIGN: A cluster-randomised non-inferiority community trial. SETTING: Health sub-centres and home deliveries in the Bijapur district of Karnataka, India. POPULATION: Women with low-risk pregnancies who were eligible for delivery with an Auxiliary Nurse Midwife at home or sub-centre and who consented to be part of the study. METHODS: Auxiliary Nurse Midwifes were randomised to secondary prevention using 800 mcg sublingual misoprostol administered to women with postpartum blood loss ≥350 ml or to universal prophylaxis using 600 mcg oral misoprostol administered to all women during the third stage of labour. MAIN OUTCOME MEASURES: Postpartum haemoglobin ≤7.8 g/dl, mean postpartum blood loss and postpartum haemoglobin, postpartum haemorrhage rate, transfer to higher-level facilities, acceptability and feasibility of the intervention. RESULTS: Misoprostol was administered to 99.7% of women as primary prevention. In secondary prevention, 92 (4.7%) women had postpartum bleeding ≥350 ml, of which 90 (97.8%) received misoprostol. The proportion of women with postpartum haemoglobin ≤7.8 g/dl was 5.9 and 8.8% in secondary and primary prevention clusters, respectively [difference -2.9%, one-sided 95% confidence interval (CI) <1.3%]. Postpartum transfer and haemorrhage rates were low (<1%) in both groups. Shivering was more common in primary prevention clusters (P = 0.013). CONCLUSION: Secondary prevention of postpartum haemorrhage with misoprostol is non-inferior to universal prophylaxis based on the primary outcome of postpartum haemoglobin. Secondary prevention could be a good alternative to universal prophylaxis as it medicates fewer women and is an acceptable and feasible strategy at the community level. TWEETABLE ABSTRACT: Secondary prevention of postpartum haemorrhage with misoprostol is non-inferior to universal prophylaxis.

A color-coded tape for uterine height measurement: a tool to identify preterm pregnancies in low resource settings.

INTRODUCTION: Neonatal mortality associated with preterm birth can be reduced with antenatal corticosteroids (ACS), yet <10% of eligible pregnant women in low-middle income countries. The inability to accurately determine gestational age (GA) leads to under-identification of high-risk women who could receive ACS or other interventions. To facilitate better identification in low-resource settings, we developed a color-coded tape for uterine height (UH) measurement and estimated its accuracy identifying preterm pregnancies. METHODS: We designed a series of colored-coded tapes with segments corresponding to UH measurements for 20-23.6 weeks, 24.0-35.6 weeks, and >36.0 weeks GA. In phase 1, UH measurements were collected prospectively in the Democratic Republic of Congo, India and Pakistan, using distinct tapes to address variation across regions and ethnicities. In phase 2, we tested accuracy in 250 pregnant women with known GA from early ultrasound enrolled at prenatal clinics in Argentina, India, Pakistan and Zambia. Providers masked to the ultrasound GA measured UH. Receiver operating characteristics (ROC) analysis was conducted. RESULTS: 1,029 pregnant women were enrolled. In all countries the tapes were most effective identifying pregnancies between 20.0-35.6 weeks, compared to the other GAs. The ROC areas under the curves and 95% confidence intervals were: Argentina 0.69 (0.63, 0.74); Zambia 0.72 (0.66, 0.78), India 0.84 (0.80, 0.89), and Pakistan 0.83 (0.78, 0.87). The sensitivity and specificity (and 95% confidence intervals) for identifying pregnancies between 20.0-35.6 weeks, respectively, were: Argentina 87% (82%-92%) and 51% (42%-61%); Zambia 91% (86%-95%) and 50% (40%-60%); India 78% (71%-85%) and 89% (83%-94%); Pakistan 63% (55%-70%) and 94% (89%-99%). CONCLUSIONS: We observed moderate-good accuracy identifying pregnancies ≤ 35.6 weeks gestation, with potential usefulness at the community level in low-middle income countries to facilitate the preterm identification and interventions to reduce preterm neonatal mortality. Further research is needed to validate these findings on a population basis.

Prevention of postpartum haemorrhage with sublingual misoprostol or oxytocin: a double-blind randomised controlled trial.

OBJECTIVE: Sublingual misoprostol produces a rapid peak concentration, and is more effective than oral administration. We compared the postpartum measured blood loss with 400 µg powdered sublingual misoprostol and after standard care using 10 iu intramuscular (IM) oxytocin. DESIGN: Double-blind randomised controlled trial. SETTING: A teaching hospital: J N Medical College, Belgaum, India. SAMPLE: A cohort of 652 consenting eligible pregnant women admitted to the labour room. METHODS: Subjects were assigned to receive the study medications and placebos within 1 minute of clamping and cutting the cord by computer-generated randomisation. Chi-square and bootstrapped Student's t-tests were used to test categorical and continuous outcomes, respectively. MAIN OUTCOME MEASURES: Measured mean postpartum blood loss and haemorrhage (PPH, loss ≥ 500 ml), >10% pre- to post-partum decline in haemoglobin, and reported side effects. RESULTS: The mean blood loss with sublingual misoprostol was 192 ± 124 ml (n=321) and 366 ± 136 ml with oxytocin IM (n=331, P ≤ 0.001). The incidence of PPH was 3.1% with misoprostol and 9.1% with oxytocin (P=0.002). No woman lost ≥ 1000 ml of blood. We observed that 9.7% and 45.6% of women experienced a haemoglobin decline of >10% after receiving misoprostol and oxytocin, respectively (P ≤ 0.001). Side effects were significantly greater in the misoprostol group than in the oxytocin group. CONCLUSION: Unlike other studies, this trial found sublingual misoprostol more effective than intramuscular oxytocin in reducing PPH, with only transient side effects being greater in the misoprostol group. The sublingual mode and/or powdered formulation may increase the effectiveness of misoprostol, and render it superior to injectable oxytocin for the prevention of PPH. Further research is needed to confirm these results.

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 Student's 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.

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 >or= 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 ANM's 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.

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 drug's low cost, ease of administration, stability, and a positive safety profile make it a good option in resource-poor settings.