Reliability and validity of last menstrual period for gestational age estimation in a low-to-middle-income setting.

AIM: Gestational age estimation by ultrasonography is the gold standard for dating pregnancies. However, the availability of prenatal ultrasonography in low-to-middle-income countries is limited. This study aimed to assess the reliability and validity of last menstrual period (LMP) as a gestational age dating method among women in Johannesburg, South Africa. METHODS: A total of 741 pregnant women were enrolled into a longitudinal study (June 2013 to July 2016). Gestational age was determined by LMP and ultrasonography. Differences in ultrasound-based and LMP-based gestational age estimates were assessed according to the American College of Obstetrics and Gynecologists' guidelines and women were classified as having discrepant results or not. Multiple statistical analyses determined the level of agreement between the two methods and validity of LMP estimates. RESULTS: Compared to ultrasound, dating by LMP assessed gestational age as 0.2 days longer. Women with discrepant results were of significantly lower weight and household socioeconomic status than those without discrepancies. While there was a substantial agreement (k = 0.64; 95% confidence interval, CI: 0.54, 0.71, P < 0.001) between the two methods, LMP only had a 29.0% (95% CI: 14.2, 48.0) sensitivity in identifying late-term neonates and a 33.3% (95% CI: 4.33, 77.7) sensitivity in identifying post-term neonates. CONCLUSION: In the absence of ultrasound, LMP is a reliable alternative for gestational age dating during early pregnancy. However, it is not sensitive in identifying late- and post-term pregnancies and should not be relied upon to make clinical decisions regarding elective cesarean section or induction of labor for supposed prolonged pregnancies.

Serotype-Specific Cell-Mediated Immunity Associated With Clearance of Homotypic Group B Streptococcus Rectovaginal Colonization in Pregnant Women.

We investigated the association between group B Streptococcus (GBS) serotype-specific capsular polysaccharide cellular immunity, measured with enzyme-linked immunospot (ELISPOT) interferon γ release assay at 20 weeks gestation in pregnant women, and its effect on rectovaginal serotype-specific GBS colonization up to 37 weeks gestation. Among women colonized by serotype III at enrollment, interferon γ ELISPOT positivity was more common in those in whom colonization was cleared (44.4%) than in those in whom colonization persisted (7.4%; P = .008), with a similar trend observed for serotype Ia. Presence of serotype-specific capsular polysaccharide cell-mediated immunity contributes to the clearance of GBS rectovaginal colonization.

Neutrophil gelatinase-associated lipocalin as a diagnostic marker of acute kidney injury in pre-eclampsia.

AIM: Neutrophil gelatinase-associated lipocalin (NGAL) is an emerging biomarker for early diagnosis of acute kidney injury (AKI). This study investigated the use of urinary NGAL as a marker of AKI in women with pre-eclampsia. METHODS: Urine and serum samples were collected over 24 h from 78 healthy and 109 pre-eclamptic women, with baseline samples taken at admission to the maternity unit; NGAL was assayed in serial urine samples. RESULTS: Baseline neutrophil gelatinase-associated lipocalin did not differ significantly between women who were healthy, those with pre-eclampsia, or with AKI (P = 0.55 for trend). When the pre-eclamptic group was divided into those with eclampsia (median, 60.5 ng/mL; IQR, 23.4-173 ng/mL; n = 19), uncomplicated pre-eclampsia (median, 18.8 ng/mL; IQR, 7.5-52.8 ng/mL; n = 48; P < 0.05 vs eclampsia), imminent eclampsia (median, 30.7 ng/mL; IQR, 13.9-49.3 ng/mL; n = 22) and pre-eclampsia with acute kidney injury (median, 60.3 ng/mL; IQR, 23.5-159 ng/mL, n = 14), however, NGAL level did differ. On multivariate regression analysis, the only significant correlate of NGAL level was the presence of eclampsia (beta = 0.22, P < 0.05). On receiver operating characteristic curve analysis, baseline NGAL did not discriminate between subjects with or without AKI (area under the curve, 0.61; 95%CI: 0.43-0.78; P = 0.12). CONCLUSION: Neutrophil gelatinase-associated lipocalin level at baseline and over a 24-h period does not provide a suitable diagnostic test for AKI in pre-eclamptic subjects.

Increased risk for group B Streptococcus sepsis in young infants exposed to HIV, Soweto, South Africa, 2004-2008(1).

Although group B Streptococcus (GBS) is a leading cause of severe invasive disease in young infants worldwide, epidemiologic data and knowledge about risk factors for the disease are lacking from low- to middle-income countries. To determine the epidemiology of invasive GBS disease among young infants in a setting with high maternal HIV infection, we conducted hospital-based surveillance during 2004-2008 in Soweto, South Africa. Overall GBS incidence was 2.72 cases/1,000 live births (1.50 and 1.22, respectively, among infants with early-onset disease [EOD] and late-onset [LOD] disease). Risk for EOD and LOD was higher for HIV-exposed than HIV-unexposed infants. GBS serotypes Ia and III accounted for 84.0% of cases, and 16.9% of infected infants died. We estimate that use of trivalent GBS vaccine (serotypes Ia, Ib, and III) could prevent 2,105 invasive GBS cases and 278 deaths annually among infants in South Africa; therefore, vaccination of all pregnant women in this country should be explored.

Evaluation of Trans-Vag broth, colistin-nalidixic agar, and CHROMagar StrepB for detection of group B Streptococcus in vaginal and rectal swabs from pregnant women in South Africa.

Maternal vaginal colonization with group B streptococcus (GBS) is a major risk factor for invasive GBS infection in newborns. The CDC-recommended method for detecting GBS colonization is to culture vaginal and rectal swabs in a selective broth followed by subculture on blood agar or a selective medium. A high incidence of antimicrobial resistance in the fecal microflora can compromise the recovery of GBS from the selective broth. Here, we compared CHROMagar StrepB (CA), Columbia colistin-nalidixic agar (CNA), and Trans-Vag selective broth enrichment for the isolation of GBS from 130 vaginal and 130 rectal swabs from pregnant women. The swabs were randomized for plating first on either CA or CNA, and they then were inoculated in Trans-Vag broth. GBS was cultured from 37.7% of the vaginal swabs and 33.1% of the rectal swabs. There were no differences in the detection rates for the vaginal swabs between CA (31.5%), CNA (26.2%), and the selective broth (30.0%). The sensitivities in relation to a composite score were 83.7%, 69.4%, and 79.6%, respectively. However, recovery of GBS from the rectal swabs was significantly higher from CA (29.2%; P<0.0001) and CNA (23.8%; P=0.002) than from the selective broth (9.2%). The sensitivities were 88.4%, 72.1%, and 27.9%, respectively. The order of plating on the solid medium was significant (P=0.003), with GBS detection rates of 30.8% and 24.6% when swabs were plated first and second, respectively. These findings show that a selective broth is not suitable for the recovery of GBS from rectal swabs in settings such as ours, due to masking of the GBS colonies by persistent microflora.

Stillbirths: what difference can we make and at what cost?

Worldwide, 2·65 million (uncertainty range 2·08 million to 3·79 million) stillbirths occur yearly, of which 98% occur in countries of low and middle income. Despite the fact that more than 45% of the global burden of stillbirths occur intrapartum, the perception is that little is known about effective interventions, especially those that can be implemented in low-resource settings. We undertook a systematic review of randomised trials and observational studies of interventions which could reduce the burden of stillbirths, particularly in low-income and middle-income countries. We identified several interventions with sufficient evidence to recommend implementation in health systems, including periconceptional folic acid supplementation or fortification, prevention of malaria, and improved detection and management of syphilis during pregnancy in endemic areas. Basic and comprehensive emergency obstetric care were identified as key effective interventions to reduce intrapartum stillbirths. Broad-scale implementation of intervention packages across 68 countries listed as priorities in the Countdown to 2015 report could avert up to 45% of stillbirths according to a model generated from the Lives Saved Tool. The overall costs for these interventions are within the general estimates of cost-effective interventions for maternal care, especially in view of the effects on outcomes across maternal, fetal, and neonatal health.

Stillbirths: how can health systems deliver for mothers and babies?

The causes of stillbirths are inseparable from the causes of maternal and neonatal deaths. This report focuses on prevention of stillbirths by scale-up of care for mothers and babies at the health-system level, with consideration for effects and cost. In countries with high mortality rates, emergency obstetric care has the greatest effect on maternal and neonatal deaths, and on stillbirths. Syphilis detection and treatment is of moderate effect but of lower cost and is highly feasible. Advanced antenatal care, including induction for post-term pregnancies, and detection and management of hypertensive disease, fetal growth restriction, and gestational diabetes, will further reduce mortality, but at higher cost. These interventions are best packaged and provided through linked service delivery methods tailored to suit existing health-care systems. If 99% coverage is reached in 68 priority countries by 2015, up to 1·1 million (45%) third-trimester stillbirths, 201 000 (54%) maternal deaths, and 1·4 million (43%) neonatal deaths could be saved per year at an additional total cost of US$10·9 billion or $2·32 per person, which is in the range of $0·96-2·32 for other ingredients-based intervention packages with only recurrent costs.

Advanced preformulation investigations for the development of a lead intravaginal bioadhesive polymeric device.

CONTEXT AND OBJECTIVE: To screen various polymers through extensive preformulation investigations to ultimately obtain a lead polymer combination for designing a desirable Intravaginal Bioadhesive Polymeric Device (IBPD). MATERIALS AND METHODS: Hydrophilic and hydrophobic polymers (18) at different combinations were blended and compressed into 62 caplet-shaped devices at 5 tons, one of the hydrophilic polymers being a modified synthetic product of polyamide 6,10 ((m)PA 6,10). Two sets of crosslinked PAA-based caplets comprising either allyl-sucrose (AS-PAA) or allyl-penta-erythritol (APE-PAA) were explored. The devices were subjected to in-process validation tests and thereafter to preformulation investigational screening {equilibrium swelling ratio (ESR) being a screening parameter}, using a One Variable at a Time (OVAT) approach. Molecular mechanics force field simulations in both vacuum and solvated systems were conducted to investigate the influence of addition and subsequent replacement of a polymer(s) on the spatial disposition and energetic profile of the sterically constrained and geometrically optimized multi-polymeric complex, IBPD. RESULTS AND DISCUSSION: The developed devices were sufficiently strong (longitudinal crushing force:286 ± 0.01 N; mean weight:600 ± 0.48 mg; mean friability:0.31 ± 0.04%). Through OVAT approach, 15 lead formulations with minimal swelling tendencies (ESRs ranging from 0.011 to 0.084) were obtained out of 62 formulations. F62 {i.e. (m)PA 6,10, (150 mg), PLGA (400 mg), EC (200 mg), PVA (25 mg) and PAA (25 mg)} displayed minimal swelling tendency and therefore the highest stability. The highly stabilized conformation of the final in silico IBPD polymeric assembly PLGA-(m)PA6,10-PVA-PAA-EC corroborated the experimental results in terms of preformulation investigational screening using the OVAT approach. CONCLUSION: The results obtained suggest that (m)PA 6,10, PLGA, EC, PVA and PAA at an appropriate weight ratio may be suitable for development of an IBPD.

Optimization of a polymer composite employing molecular mechanic simulations and artificial neural networks for a novel intravaginal bioadhesive drug delivery device.

This study aimed at elucidating an optimal synergistic polymer composite for achieving a desirable molecular bioadhesivity and Matrix Erosion of a bioactive-loaded Intravaginal Bioadhesive Polymeric Device (IBPD) employing Molecular Mechanic Simulations and Artificial Neural Networks (ANN). Fifteen lead caplet-shaped devices were formulated by direct compression with the model bioactives zidovudine and polystyrene sulfonate. The Matrix Erosion was analyzed in simulated vaginal fluid to assess the critical integrity. Blueprinting the molecular mechanics of bioadhesion between vaginal epithelial glycoprotein (EGP), mucin (MUC) and the IBPD were performed on HyperChem 8.0.8 software (MM+ and AMBER force fields) for the quantification and characterization of correlative molecular interactions during molecular bioadhesion. Results proved that the IBPD bioadhesivity was pivoted on the conformation, orientation, and poly(acrylic acid) (PAA) composition that interacted with EGP and MUC present on the vaginal epithelium due to heterogeneous surface residue distributions (free energy= -46.33 kcalmol(-1)). ANN sensitivity testing as a connectionist model enabled strategic polymer selection for developing an IBPD with an optimally prolonged Matrix Erosion and superior molecular bioadhesivity (ME = 1.21-7.68%; BHN = 2.687-4.981 N/mm(2)). Molecular modeling aptly supported the EGP-MUC-PAA molecular interaction at the vaginal epithelium confirming the role of PAA in bioadhesion of the IBPD once inserted into the posterior fornix of the vagina.

Investigation of the physicochemical and physicomechanical properties of a novel intravaginal bioadhesive polymeric device in the pig model.

The purpose of this study was to develop and evaluate the bioadhesivity, in vitro drug release, and permeation of an intravaginal bioadhesive polymeric device (IBPD) loaded with 3'-azido-3'-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Modified polyamide 6,10, poly(lactic-coglycolic acid), polyacrylic acid, polyvinyl alcohol, and ethylcellulose were blended with model drugs AZT and PSS as well as radio-opaque barium sulfate (BaSO4) and then compressed into caplet devices on a tableting press. One set of devices was coated with 2% w/v pentaerythritol polyacrylic acid (APE-PAA) while another remained uncoated. Thermal analysis was performed on the constituent polymers as well the IBPD. The changes in micro-environmental pH within the simulated human vaginal fluid due to the presence of the IBPD were assessed over a period of 30 days. Textural profile analysis indicated that the bioadhesivity of the APE-PAA-coated devices (3.699 +/- 0.464 N; 0.0098 +/- 0.0004 J) was higher than that of the uncoated devices (1.198 +/- 0.150 N; 0.0019 +/- 0.0001 J). In addition, BaSO4-facilitated X-ray imaging revealed that the IBPD adhered to pig vaginal tissue over the experimental period of 30 days. Controlled drug release kinetics was obtained over 72 days. During a 24-h permeation study, an increase in drug flux for both AZT (0.84 mg cm(-2) h(-1)) and PSS (0.72 mg cm(-2) h(-1)) was realized up to 12 h and thereafter a steady-state was achieved. The diffusion and dissolution dynamics were mechanistically deduced based on a chemometric and molecular structure modeling approach. Overall, results suggested that the IBPD may be sufficiently bioadhesive with desirable physicochemical and physicomechanical stability for use as a prolonged intravaginal drug delivery device.

Implementation of a PMTCT programme in a high HIV prevalence setting in Johannesburg, South Africa: 2002-2015.

BACKGROUND: Great strides have been made in decreasing paediatric human immunodeficiency virus (HIV) infections, especially in sub-Saharan Africa. In South Africa, new paediatric HIV infections decreased by 84% between 2009 and 2015. This achievement is a result of a strong political will and the rapid evolution of the country's prevention of mother-to-child transmission (PMTCT) guidelines. OBJECTIVES: In this paper we report on the implementation of a large PMTCT programme in Soweto, South Africa. METHODS: We reviewed routinely collected PMTCT data from 13 healthcare facilities, for the period 2002-2015. Antiretroviral therapy (ART) coverage among pregnant women living with HIV (PWLHIV) and the mother-to-child transmission (MTCT) rate at early infant diagnosis were evaluated. RESULTS: In total, 360 751 pregnant women attended the facilities during the review period, and the HIV prevalence remained high throughout at around 30%. The proportion of PWLHIV presenting with a known HIV status increased from 14.3% in 2009 when the indicator was first collected to 45% in 2015, p < 0.001. In 2006, less than 10% of the PWLHIV were initiated on ART, increasing to 88% by 2011. The MTCT rate decreased from 6.9% in 2007 to under 1% from 2013 to 2015, p < 0.001. CONCLUSION: The achievements in decreasing paediatric HIV infections have been hailed as one of the greatest public health achievements of our times. While there are inherent limitations with using routinely collected aggregate data, the Soweto data reflect progress made in the implementation of PMTCT programmes in South Africa. Progress with PMTCT has, however, not been accompanied by a decline in HIV prevalence among pregnant women.

Role of a second stage partogram in predicting the outcome of normal labour.

BACKGROUND: Management of the second stage of labour is dictated by arbitrary time limits rather than true measures of progress. No partogram is available for second stage of labour. OBJECTIVES: To evaluate a partogram designed for use for the second stage of labour. METHODS: This prospective cross-sectional analytical study included low-risk pregnant women with singleton fetuses with vertex presentations at term. From onset of the second stage, vaginal examinations were performed every 30 min until delivery. A scoring system developed by Sizer et al. was used based on station and position of fetal head. Scores were plotted on a second stage partogram and used to predict labour outcomes, such as duration of second stage and mode of delivery. RESULTS: Of 79 women examined, 73 had spontaneous vaginal delivery. Of the remaining six, four required oxytocin infusion and other two required vacuum extraction. The median durations of the second stage of labour for primigravidas (n = 34) and multigravidas (n = 45) were 35 and 25 min, respectively. The median Sizer's partogram score at the onset of second stage was 4. Multiple regression analysis showed that the partogram score (r2 = 0.27) and gravidity (r2 = 0.10) were independent predictors of duration of the second stage. There was a significant association between second stage progress plotted to the right of the partogram line and non-spontaneous delivery (P = 0.01). CONCLUSION: The second stage partogram score at onset can predict the duration of second stage. Poor progress plotted on the partogram is associated with non-spontaneous delivery.

Accuracy of five plasma calibrated glucometers to screen for and diagnose gestational diabetes mellitus in a low resource clinic setting.

AIMS: We investigated the clinical and analytic accuracy of five plasma calibrated glucometers, the use of which is advocated by the World Health Organisation and the International Federation of Gynaecology and Obstetrics, to screen for and diagnose gestational diabetes mellitus (GDM) in low resource settings. METHODS: 592 consecutive black African women underwent a 75 g oral glucose tolerance test (OGTT) at 24-28 weeks gestation at an urban South African community health clinic. Capillary glucose was measured by one of five glucometer brands, each paired with a routine laboratory hexokinase method of plasma glucose measurement. The laboratory results served as the gold standard reference test for GDM diagnosis. World Health Organisation GDM diagnostic thresholds were applied to glucometer and laboratory results. RESULTS: Glucometer and laboratory determined GDM prevalence was 75/592 (12.7%) and 30/592 (5.1%) with an elevated fasting glucose diagnostic in 64/75 (85%) and 24/30 (80%) of cases respectively. The proportion of glucometer results fulfilling ISO 15197:2013 recommended analytic accuracy at fasting, 60, and 120 min of the OGTT was 92.4%, 49.8% and 61.5%, with Bland Altman method revealing a positive glucometer bias of 0.22 mmol/l (-0.69-1.12 mmol/l), 0.96 mmol/l (-0.65-2.56 mmol/l) and 0.73 mmol/l (-0.73-2.19 mmol/l) respectively. Only three of the glucometer brands evaluated fulfilled ISO 15197:2013 analytic accuracy requirements and this was only achieved at fasting. All glucometers tested were inaccurate at one and two hours of the OGTT. CONCLUSIONS: Not all glucometers may be suitable for GDM screening as only three were accurate compared to the reference test and then only at fasting of the OGTT. Importantly, laboratory fasting glucose was diagnostic of GDM in 80% of cases in this study population.

The impact of differences in plasma glucose between glucose oxidase and hexokinase methods on estimated gestational diabetes mellitus prevalence.

We evaluated the extent of measurement discordance between glucose oxidase and hexokinase laboratory methods and the effect of this on estimated gestational diabetes mellitus (GDM) prevalence in a routine clinical setting. 592 consecutive urban African women were screened for GDM. Paired venous specimens were submitted to two independent calibrated laboratories that used either method to measure plasma glucose concentrations. World Health Organisation diagnostic criteria were applied. GDM prevalence determined by the glucose oxidase and hexokinase methods was 6.9% and 5.1% respectively. The overall GDM prevalence was 9%. Only 34% of GDM positive diagnoses were common to both laboratory methods. Bland Altman plots identified a bias of 0.2 mmol/l between laboratory methods. Plasma glucose concentrations measured by the glucose oxidase method were more platykurtic in distribution. Low diagnostic agreement between laboratory methods was further indicated by a Cohen's kappa of 0.48 (p < 0.001). Reports of GDM prevalence using either the glucose oxidase or hexokinase laboratory methods may not be truly interchangeable or directly comparable.

Sagittal suture overlap in cephalopelvic disproportion: blinded and non-participant assessment.

OBJECTIVE: To determine the role of assessment of overlap of fetal skull bones (molding) in intrapartum prediction of cephalopelvic disproportion (CPD). DESIGN: Prospective cross-sectional study. SETTING: South African high-risk obstetric unit that receives referrals from other facilities. POPULATION: Women of at least 37 weeks' gestation in the active phase of labor, with singleton vertex presentations and live fetuses, and without previous cesarean sections. METHOD: The researcher was blinded to parity and previous clinical information on the women, and not involved in their obstetric care. The researcher performed clinical assessments, including estimation of level of head, cervical dilatation, head flexion, position, overlap of fetal skull bones, caput succedaneum and asynclitism. A single assessment was done on each woman. MAIN OUTCOME MEASURE: CPD, defined as cesarean section for poor progress in labor. RESULTS: The author examined 504 women, and CPD occurred in 113 (22.4%). In multivariate logistic regression analysis, sagittal suture overlap was independently associated with CPD. Other factors associated were maternal height, duration of labor, birth weight, and the interaction between caput succedaneum and cervical dilatation at the time of examination. Lambdoid suture overlap was not significantly associated with CPD, and could be determined in only 66.5% of examinations because of frequent head deflexion. CONCLUSION: Assessment of sagittal suture overlap, but not lambdoid suture overlap, is useful for prediction of CPD. Knowledge of sagittal suture overlap may assist in decisions on clinical management where there is poor progress in a trial of labor.

Interobserver agreement in intrapartum estimation of fetal head station.

OBJECTIVE: To determine interobserver agreement in estimation of fetal head station during labor, and the determinants of agreement. METHODS: A prospective study of fetal head station in 508 women in term labor. Vaginal examination of station was performed by a researcher at the same time as clinicians performed routine intrapartum assessments of the participants. Station 0 was considered to represent engagement. RESULTS: Station could be estimated by both the researcher and clinicians in 446 women (88%). The kappa statistic for agreement was 0.23 (95% confidence interval, 0.17-0.29). There was agreement in 166 cases (37%) and disagreement by 1 cm in 208 (47%) cases. Agreement was best (50%) when the researcher assessed the head at station minus 1. Multiple regression analysis showed that agreement was not influenced by level of experience of the attending clinicians, nor by obstetric factors. CONCLUSION: Estimation of station as a method of determining the level of the fetal head in labor appears imprecise and poorly reproducible.

A review of current intravaginal drug delivery approaches employed for the prophylaxis of HIV/AIDS and prevention of sexually transmitted infections.

The objective of this review is to describe the current status of several intravaginal anti-HIV microbicidal delivery systems these delivery systems and microbicidal compounds in the context of their stage within clinical trials and their potential cervicovaginal defence successes. The global Human Immuno-Deficiency Virus (HIV) pandemic continues to spread at a rate of more than 15,000 new infections daily and sexually transmitted infections (STIs) can predispose people to acquiring HIV infection. Male-to-female transmission is eight times more likely to occur than female-to-male transmission due to the anatomical structure of the vagina as well as socio-economic factors and the disempowerment of women that renders them unable to refuse unsafe sexual practices in some communities. The increased incidence of HIV in women has identified the urgent need for efficacious and safe intravaginal delivery of anti-HIV agents that can be used and controlled by women. To meet this challenge, several intravaginal anti-HIV microbicidal delivery systems are in the process of been developed. The outcomes of three main categories are discussed in this review: namely, dual-function polymeric systems, non-polymeric systems and nanotechnology-based systems. These delivery systems include formulations that modify the genital environment (e.g. polyacrylic acid gels and lactobacillus gels), surfactants (e.g. sodium lauryl sulfate), polyanionic therapeutic polymers (e.g. carageenan and carbomer/lactic acid gels), proteins (e.g. cyanovirin-N, monoclonal antibodies and thromspondin-1 peptides), protease inhibitors and other molecules (e.g. dendrimer based-gels and the molecular condom). Intravaginal microbicide delivery systems are providing a new option for preventing the transmission of STIs and HIV.

A systematic review of maternal near miss and mortality due to postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage (PPH) is the principal direct cause of maternal mortality worldwide. Analysis of maternal near miss could increase understanding of survival among women with life-threatening PPH. OBJECTIVES: To determine the near-miss ratio and maternal mortality index for PPH globally. SEARCH STRATEGY: A prevalence systematic review was conducted of English-language articles published from 1995 to 2014. Suitable articles were identified from the Scopus, PubMed, Embase, and Grey Literature databases. The main search terms used were "maternal near-miss" and "severe acute maternal morbidity." SELECTION CRITERIA: Near-miss studies and audits describing the severe maternal outcome rate for PPH were included. DATA COLLECTION AND ANALYSIS: Data were extracted from eligible publications. Quantitative analysis and narrative synthesis were used. MAIN RESULTS: For 26 included studies, the median near-miss ratio for PPH was 3 per 1000 live births. The mortality index for PPH was 6.6% (range 0.0%-40.7%). The mortality index was highest in low-income countries and lower middle-income countries. Overall, PPH was the most frequent contributor to obstetric hemorrhage, with atonic uterus identified as the main cause. CONCLUSIONS: Women in low-income countries and lower middle-income countries have an increased likelihood of severe PPH and of dying from PPH-related consequences.

Submicron Matrices Embedded in a Polymeric Caplet for Extended Intravaginal Delivery of Zidovudine.

In this study, an intravaginal delivery system able to deliver an anti-HIV-1 agent for the purpose of potentially reducing HIV-1 transmission acting over an extended duration was successfully formulated. This delivery system was a composite polymeric caplet comprising zidovudine-loaded polyethylene glycol enclatherated pectin-mucin submicron matrices embedded within a poly (D,L-lactide), magnesium stearate, Kollidon® SR, and Carbopol® 974P NF-based polymeric caplet matrix. A three-factor and three-level Box-Behnken statistical design was utilized to optimize the polymeric caplet. The optimized directly compressed composite polymeric caplet hardness was 22.1 ± 0.3 N and the matrix resilience was 62.4 ± 0.6%. The swelling- and diffusion-controlled fractional zidovudine (AZT) release from the optimized caplet was 0.74 ± 0.01 in simulated vaginal fluid (SVF), which increased to 0.81 ± 0.21 in phosphate-buffered saline (PBS) simulating seminal fluid, over 30 days. Caplet matrix swelling was directly related to the percentage Carbopol 974P NF composition. An intravaginal system for AZT delivery was tested in the pig model over 28 days. X-ray analysis depicted delivery system swelling with matrix contrast fading over time as vaginal fluid permeated the matrix core. Plasma, vaginal fluid swab eluates, and tissue AZT concentrations were measured by gradient ultra-performance liquid chromatography (UPLC)-tandem photodiode array detection. Vaginal tissue and vaginal fluid swab eluate AZT concentrations remained above effective levels over 28 days and were higher than plasma AZT concentrations, availing a system with reduced systemic toxicity and more effective inhibition of viral replication at the site of entry.