Advancing maternal survival in the global context: are our strategies working?

There have been significant gains in improving maternal mortality over the last two decades. Researchers have suggested a variety of interventions and mechanisms to explain these improvements. While it is likely that much of what has been done in research and programs has contributed to this decline, the evidence regarding what works in the settings in which women deliver continues to face many challenges. We review the evidence for these improvements and suggest that there remain areas to focus on, particularly the births which currently take place in an unsupervised or substandard environments. We highlight the main areas where more evidence is needed, and end with a call to determine which of our interventions seem to have the most benefit; which do not; and where to invest future resources

Oxytocin via Uniject (a prefi lled single-use injection) versus oral misoprostol for prevention of postpartum haemorrhage at the community level: a cluster-randomised controlled trial

Background Access to injectable uterotonics for management of postpartum haemorrhage remains limited in Senegal outside health facilities, and misoprostol and oxytocin delivered via Uniject have been deemed viable alternatives in community settings. We aimed to compare the effi cacy of these drugs when delivered by auxiliary midwives at maternity huts. Methods We did an unmasked cluster-randomised controlled trial at maternity huts in three districts in Senegal. Maternity huts with auxiliary midwives located 3–21 km from the closest referral centre were randomly assigned (1:1; via a computer-generated random allocation overseen by Gynuity Health Projects) to either 600 μg oral misoprostol or 10 IU oxytocin in Uniject (intramuscular), stratifi ed by reported previous year clinic volume (deliveries) and geographical location (inland or coastal). Maternity huts that had been included in a previous study of misoprostol for prevention of postpartum haemorrhage were excluded to prevent contamination. Pregnant women in their third trimester were screened for eligibility either during community outreach or at home-based prenatal visits. Only women delivered by the auxiliary midwives in the maternity huts were eligible for the study. Women with known allergies to prostaglandins or pregnancy complications were excluded. The primary outcome was mean change in haemoglobin concentration measured during the third trimester and after delivery. This study was registered with ClinicalTrials.gov, number NCT01713153. Findings 28 maternity hut clusters were randomly assigned—14 to the misoprostol group and 14 to the oxytocin group. Between June 6, 2012, and Sept 21, 2013, 1820 women were recruited. 647 women in the misoprostol group and 402 in the oxytocin group received study drug and had recorded pre-delivery and post-delivery haemoglobin concentrations, and overall 1412 women delivered in the study maternity huts. The mean change in haemoglobin concentrations was 3·5 g/L (SD 16·1) in the misoprostol group and 2·7 g/L (SD 17·8) in the oxytocin group. When adjusted for cluster design, the mean diff erence in haemoglobin decreases between groups was not signifi cant (0·3 g/L, 95% CI –8·26 to 8·92, p=0·71). Both drugs were well tolerated. Shivering was common in the misoprostol group, and nausea in the oxytocin group. Postpartum haemorrhage was diagnosed in one woman allocated to oxytocin, who was referred and transferred to a higher-level facility for additional care, and fully recovered. No other women were transferred. Interpretation In terms of eff ects on haemoglobin concentrations, neither oxytocin nor misoprostol was signifi cantly better than the other, and both drugs were safe and effi cacious when delivered by auxiliary midwives. The programmatic limitations of oxytocin, including short shelf life outside the cold chain, mean that misoprostol could be more appropriate for community-level prophylaxis of postpartum haemorrhage

Reproductive health services in KwaZulu Natal, South Africa: A situation analysis study focusing on HIV/AIDS services

This Horizons report examines the readiness of reproductive health services in South Africa, which are primarily geared to women, to deliver HIV and AIDS treatment, care, and prevention services. The goal of the study was to obtain information from a representative sample of provincial health care facilities offering reproductive health services in KwaZulu Natal to meet the growing demand for HIV/AIDS-related services. Ninety-eight hospitals, community health centers, and clinics participated in the situation analysis that identified gaps in service delivery and determined priorities for service integration. Results of the study were presented to a large audience of Department of Health, NGO, and donor agency staff with the hope that this workshop would set a trend for feedback and the use of research for service improvement

Methylmalonic acidemia (MMA) in pregnancy: a case series and literature review

IntroductionWomen with inherited metabolic disorders, including those with previously life‐limiting conditions such as MMA, are reaching child‐bearing age more often due to advances in early diagnosis and improved pediatric care. Information surrounding maternal and fetal complications associated with the underlying disorders remains largely unexplored.MethodsPregnancies affected by maternal MMA were ascertained through study 04‐HG‐0127 “Clinical and Basic Investigations of Methylmalonic Acidemia and Related Disorders” (clinicaltrials.gov identifier: NCT00078078) and via literature review. Prenatal and delivery records in study participants were reviewed.ResultsSeventeen pregnancies were identified in women with isolated MMA, including three abortions, one termination, and 13 completed pregnancies [three cases with cblA (four pregnancies), four cases of mut‐ (one cobalamin responsive, three non‐responsive), five cases with unknown type of MMA]. Seventeen percent (3/17) of the pregnancies resulted in a first trimester abortion, while 38.5 % (5/13) of the completed pregnancies resulted in preterm deliveries. A cesarean delivery rate of 53.8 % (7/13) was noted among the cohort. Fetal distress or nonreassuring fetal status was the indication for 57 % (4/7) cesarean deliveries. One patient was reported to have metabolic crisis as well as episodes of mild hyperammonemia. Malformations or adverse outcomes in the progeny were not observed.ConclusionAlthough there have been a small number of pregnancies identified in women with MMA, the cumulative results suggest that the majority of pregnancies can be complicated by cesarean delivery and increased risk of prematurity. A pregnancy registry could clarify perinatal complications and define management approaches needed to ensure optimal maternal and fetal outcomes in this growing patient population.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147009/1/jimd0839.pd

Case finding and case management of chlamydia and gonorrhea infections among women: What we do and do not know

As the world grapples with the HIV pandemic, the implementation of the agenda determined by the International Conference on Population and Development (1994) at Cairo, and the matter of providing health services of adequate quality in an ethical, gender-sensitive manner, new questions are arising about how to attend to reproductive tract infections, including sexually transmitted infections (STIs), among women. This paper reviews the results of validation studies of syndromic algorithms, other nonlaboratory clinically based tools, and risk scoring for finding women infected with chlamydia and gonorrhea, particularly among those attending family planning and antenatal clinics in developing countries. The results raise challenges for policymakers in sorting through what course of action is most appropriate in a particular context. Research and policy analysis for determining the best approach for addressing chlamydia/gonorrhea infection in settings with different prevalence rates, program capacity, and sexual behavior patterns are lacking. The report concludes that simple low-cost diagnostics for use in resource-poor settings are desperately needed

Incidence of Postpartum Infection after Vaginal Delivery in Viet Nam

This study assessed the incidence of postpartum infection which is rarely clinically evaluated and is probably underestimated in developing countries. This prospective study identified infection after vaginal delivery by clinical and laboratory examinations prior to discharge from hospital and again at six weeks postpartum in Ho Chi Minh City, Viet Nam. Textbook definitions, physicians' diagnoses, symptomatic and verbal autopsy definitions were used for classifying infection. Logistic regression was used for determining associations of postpartum infection with socioeconomic and reproductive characteristics. In total, 978 consecutive, eligible consenting women were followed up at 42\ub17 (range 2-45) days postpartum (not associated with incidence). Ninety-eight percent took 'prophylactic' antibiotics. The most conservative estimate of the incidence of postpartum infection was 1.7%. The incidence of serious infection was 0.5%, but increased to 4.6% when verbal autopsy and symptomatic definitions were used. Postpartum infection, particularly serious infection, is greatly underestimated. Just preventing or treating infection could have a substantial impact on reducing maternal mortality in developing countries

Heterohexamers Formed by CcmK3 and CcmK4 Increase the Complexity of Beta Carboxysome Shells.

Bacterial microcompartments (BMCs) encapsulate enzymes within a selectively permeable, proteinaceous shell. Carboxysomes are BMCs containing ribulose-1,5-bisphosphate carboxylase oxygenase and carbonic anhydrase that enhance carbon dioxide fixation. The carboxysome shell consists of three structurally characterized protein types, each named after the oligomer they form: BMC-H (hexamer), BMC-P (pentamer), and BMC-T (trimer). These three protein types form cyclic homooligomers with pores at the center of symmetry that enable metabolite transport across the shell. Carboxysome shells contain multiple BMC-H paralogs, each with distinctly conserved residues surrounding the pore, which are assumed to be associated with specific metabolites. We studied the regulation of β-carboxysome shell composition by investigating the BMC-H genes ccmK3 and ccmK4 situated in a locus remote from other carboxysome genes. We made single and double deletion mutants of ccmK3 and ccmK4 in Synechococcus elongatus PCC7942 and show that, unlike CcmK3, CcmK4 is necessary for optimal growth. In contrast to other CcmK proteins, CcmK3 does not form homohexamers; instead CcmK3 forms heterohexamers with CcmK4 with a 1:2 stoichiometry. The CcmK3-CcmK4 heterohexamers form stacked dodecamers in a pH-dependent manner. Our results indicate that CcmK3-CcmK4 heterohexamers potentially expand the range of permeability properties of metabolite channels in carboxysome shells. Moreover, the observed facultative formation of dodecamers in solution suggests that carboxysome shell permeability may be dynamically attenuated by "capping" facet-embedded hexamers with a second hexamer. Because β-carboxysomes are obligately expressed, heterohexamer formation and capping could provide a rapid and reversible means to alter metabolite flux across the shell in response to environmental/growth conditions

The establishment of the GENEQOL consortium to investigate the genetic disposition of patient-reported quality-of-life outcomes

To our knowledge, no comprehensive, interdisciplinary initiatives have been taken to examine the role of genetic variants on patient-reported quality-of-life outcomes. The overall objective of this paper is to describe the establishment of an international and interdisciplinary consortium, the GENEQOL Consortium, which intends to investigate the genetic disposition of patient-reported quality-of-life outcomes. We have identified five primary patient-reported quality-of-life outcomes as initial targets: negative psychological affect, positive psychological affect, self-rated physical health, pain, and fatigue. The first tangible objective of the GENEQOL Consortium is to develop a list of potential biological pathways, genes and genetic variants involved in these quality-of-life outcomes, by reviewing current genetic knowledge. The second objective is to design a research agenda to investigate and validate those genes and genetic variants of patient-reported quality-of-life outcomes, by creating large datasets. During its first meeting, the Consortium has discussed draft summary documents addressing these questions for each patient-reported quality-of-life outcome. A summary of the primary pathways and robust findings of the genetic variants involved is presented here. The research agenda outlines possible research objectives and approaches to examine these and new quality-of-life domains. Intriguing questions arising from this endeavor are discussed. Insight into the genetic versus environmental components of patient-reported quality-of-life outcomes will ultimately allow us to explore new pathways for improving patient care. If we can identify patients who are susceptible to poor quality of life, we will be able to better target specific clinical interventions to enhance their quality of life and treatment outcome