Implementing effective community-based surveillance in research studies of maternal, newborn and infant outcomes in low resource settings.

BACKGROUND: Globally adopted health and development milestones have not only encouraged improvements in the health and wellbeing of women and infants worldwide, but also a better understanding of the epidemiology of key outcomes and the development of effective interventions in these vulnerable groups. Monitoring of maternal and child health outcomes for milestone tracking requires the collection of good quality data over the long term, which can be particularly challenging in poorly-resourced settings. Despite the wealth of general advice on conducting field trials, there is a lack of specific guidance on designing and implementing studies on mothers and infants. Additional considerations are required when establishing surveillance systems to capture real-time information at scale on pregnancies, pregnancy outcomes, and maternal and infant health outcomes. MAIN BODY: Based on two decades of collaborative research experience between the Kintampo Health Research Centre in Ghana and the London School of Hygiene and Tropical Medicine, we propose a checklist of key items to consider when designing and implementing systems for pregnancy surveillance and the identification and classification of maternal and infant outcomes in research studies. These are summarised under four key headings: understanding your population; planning data collection cycles; enhancing routine surveillance with additional data collection methods; and designing data collection and management systems that are adaptable in real-time. CONCLUSION: High-quality population-based research studies in low resource communities are essential to ensure continued improvement in health metrics and a reduction in inequalities in maternal and infant outcomes. We hope that the lessons learnt described in this paper will help researchers when planning and implementing their studies.

Health service provider education and/or training in infant male circumcision to improve short- and long-term morbidity outcomes: A systematic review.

AIM: To systematically review the effectiveness of education and/or training for traditional (informal) and formal health service providers in infant male circumcision on morbidity or mortality outcomes. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Global Health, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects and clinical trial registries in all languages from January 1985 to June 2018. Our primary outcomes were all-cause morbidity and all-cause mortality. RESULTS: We identified 1399 publications. Only four non-controlled before and after studies from the USA and Uganda satisfied our criteria, all of which examined the effect of training on the skills and knowledge of medical doctors, midwives and clinical officers. No study involved informal traditional circumcision providers. All included studies were low quality. CONCLUSIONS: High-quality studies of simple training packages to improve education and training of circumcision providers, especially informal non-medical providers in low income countries are needed.

Determinants of morbidity associated with infant male circumcision: community-level population-based study in rural Ghana.

OBJECTIVE: Male circumcision services have expanded throughout Africa as part of a long-term HIV prevention strategy. We assessed the effect of type of service provider (formal and informal) and hygiene practices on circumcision-related morbidities in rural Ghana. METHODS: Population-based, cross-sectional study conducted between May and December 2012 involving 2850 circumcised infant males aged under 12 weeks. Multivariable logistic regression models were adjusted for maternal age, maternal education, income, birthweight and site of circumcision. RESULTS: A total of 2850 (90.7%) infant males were circumcised. Overall, the risk of experiencing a morbidity (defined as complications occurring during or after the circumcision procedure as reported by the primary caregiver) was 8.1% (230). Risk was not significantly increased if the circumcision was performed by informal providers (121, 7.2%) vs. formal health service providers (109, 9.8%) [adjusted odds ratio (aOR) 1.11, 95% CI 0.80-1.47, P = 0.456]. Poor hygiene practices were associated with significantly increased risk of morbidity: no handwashing [148 (11.7%)] (aOR 1.78, 95% CI 1.27-2.52, P = 0.001); not cleaning circumcision instruments [174 (10.6%)] (aOR 1.80, 95% CI 1.27-2.54, P = 0.001); and uncleaned penile area [190 (10.0%)] (aOR 1.84, 95% CI 1.25-2.70, P = 0.002). CONCLUSION: The risk of morbidity after infant male circumcision in rural Ghana is high, chiefly due to poor hygiene practices. Governmental and non-governmental organisations need to improve training of circumcision providers in hygiene practices in sub-Saharan Africa.

Effect of early neonatal vitamin A supplementation on mortality during infancy in Ghana (Neovita): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Results of randomised controlled trials of newborn (age 1-3 days) vitamin A supplementation have been inconclusive. The WHO is coordinating three large randomised trials in Ghana, India, and Tanzania (Neovita trials). We present the findings of the Neovita trial in Ghana. METHODS: This study was a population-based, individually randomised, double-blind, placebo-controlled trial in the Brong Ahafo region of Ghana. The trial participants were infants aged at least 2 h, identified at home or facilities on the day of birth or in the next 2 days, able to feed orally, and likely to stay in the study area for at least 6 months. They were randomly assigned (ratio 1:1) to receive either one oral dose of vitamin A (50,000 IU) or placebo immediately after recruitment. The research team and parents of the infants were masked to treatment assignment. Follow-up home visits were undertaken every 4 weeks, when data were recorded for deaths, facility use, and care seeking. The primary outcome was post-supplementation mortality to 6 months of age. Analysis was by intention to treat. Potential adverse events were recorded at 1 and 3 days after supplementation. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR)CTRN12610000582055. FINDINGS: We assessed 26,414 livebirths for eligibility between Aug 16, 2010, and Nov 7, 2011. We recruited 22,955 newborn infants, with 11,474 randomly assigned to receive vitamin A and 11,481 to receive placebo. Loss to follow-up was low with vital status at 6 months of age reported for 22,698 (98·9%) infants. We recorded 278 post-supplementation deaths to 6 months of age in the vitamin A group (mortality risk 24·5 in 1000 supplemented infants) and 248 deaths in the placebo group (mortality risk 21·8 per 1000 supplemented infants), relative risk (RR) 1·12 (95% CI 0·95-1·33; p=0·183) and risk difference (RD) 2·66 (95% CI -1·25 to 6·57; p=0·18). Adverse events within 3 days of supplementation did not differ by trial group. 122 infants died in the first 3 days after supplementation; 70 (0·6%) in the vitamin A and 52 (0·5%) in the placebo group (risk ratio [RR] 1·35, 95% CI 0·94-1·93, p=0·102). 53 infants were reported to have a bulging fontanelle; 32 (0·3%) in the vitamin A group and 21 (0·2%) in the placebo group (RR 1·53, 0·88-2·62, p=0·130). INTERPRETATION: The results of this trial do not support inclusion of newborn vitamin A supplementation as a child survival strategy in Ghana. FUNDING: Bill & Melinda Gates Foundation grant to the WHO.

Vaccination timing of low-birth-weight infants in rural Ghana: a population-based, prospective cohort study.

OBJECTIVE: To investigate delays in first and third dose diphtheria-tetanus-pertussis (DTP1 and DTP3) vaccination in low-birth-weight infants in Ghana, and the associated determinants. METHODS: We used data from a large, population-based vitamin A trial in 2010-2013, with 22 955 enrolled infants. We measured vaccination rate and maternal and infant characteristics and compared three categories of low-birth-weight infants (2.0-2.4 kg; 1.5-1.9 kg; and < 1.5 kg) with infants weighing ≥ 2.5 kg. Poisson regression was used to calculate vaccination rate ratios for DTP1 at 10, 14 and 18 weeks after birth, and for DTP3 at 18, 22 and 24 weeks (equivalent to 1, 2 and 3 months after the respective vaccination due dates of 6 and 14 weeks). FINDINGS: Compared with non-low-birth-weight infants (n = 18 979), those with low birth weight (n = 3382) had an almost 40% lower DTP1 vaccination rate at age 10 weeks (adjusted rate ratio, aRR: 0.58; 95% confidence interval, CI: 0.43-0.77) and at age 18 weeks (aRR: 0.63; 95% CI: 0.50-0.80). Infants weighing 1.5-1.9 kg (n = 386) had vaccination rates approximately 25% lower than infants weighing ≥ 2.5 kg at these time points. Similar results were observed for DTP3. Lower maternal age, educational attainment and longer distance to the nearest health facility were associated with lower DTP1 and DTP3 vaccination rates. CONCLUSION: Low-birth-weight infants are a high-risk group for delayed vaccination in Ghana. Efforts to improve the vaccination of these infants are warranted, alongside further research to understand the reasons for the delays.

Two distinct oral routes of misoprostol in mifepristone medical abortion: a randomized controlled trial.

OBJECTIVE: To study the efficacy, safety, and acceptability of oral immediately swallowed and buccal misoprostol 800 mcg after mifepristone 200 mg for terminating pregnancy through 63 days since the last menstrual period (LMP). METHODS: This seven-site study randomly assigned 966 women seeking abortions to oral or buccal misoprostol 800 mcg 24-36 hours after mifepristone 200 mg with 7-14-day follow-up. RESULTS: Success rates in the oral and buccal groups were 91.3% (389 of 426) and 96.2% (405 of 421), respectively (P=.003; relative risk [RR] 0.95, 95% confidence interval [CI] 0.92-0.98). Ongoing pregnancy occurred in 3.5% (15 of 426) of women who took oral misoprostol compared with 1.0% (4 of 421) of women in the buccal group (P=.012; RR 3.71, 95% CI 1.24-11.07). Through 49 days since the LMP, oral and buccal regimens performed similarly, but success with oral misoprostol decreased as pregnancy advanced. In pregnancies of 57-63 days since the LMP, success with oral misoprostol fell below 90%, whereas that with buccal remained high (oral 85.1% [97 of 114], buccal 94.8% [109 of 115], P=.015, RR 0.90, 95% CI 0.82-0.98). Furthermore, in this gestational age group, there were significantly more ongoing pregnancies among women who took misoprostol orally (7.9% [9 of 114]) compared with buccally (1.7% [2 of 115]; P=.029, RR 4.54, 95% CI 1.0-20.55). Adverse effect profiles were similar, although fever and chills were reported approximately 10% more often among women who took buccal misoprostol. Satisfaction and acceptability were high for both methods. CONCLUSION: Buccal misoprostol 800 mcg after mifepristone 200 mg is a good option for medical abortion through 63 days since the LMP. Oral misoprostol 800 mcg is also a safe and effective alternative, although success rates diminish with increasing gestational age. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00386867 LEVEL OF EVIDENCE: I.

Client Perceptions of Quality and Choice at Static, Mobile Outreach, and Special Family Planning Day Services in 3 African Countries.

BACKGROUND: Use of long-acting reversible contraceptives (LARCs) has grown rapidly in the Democratic Republic of the Congo (DRC), Tanzania, and Uganda. Uptake of LARCs is particularly high during mobile outreach and special family planning day events. It is therefore important to examine client perceptions of and experiences with full, free, and informed choice (FFIC) in different service delivery modalities. METHODS: Between April and July 2015, we conducted a cross-sectional family planning client survey to assess FFIC and client satisfaction at static, mobile outreach, and special family planning day services in the DRC (n=9 sites), Tanzania (n=13), and Uganda (n=8). The study investigated clients' perceptions across 13 elements of FFIC, including measures of the quality of counseling and respondent satisfaction with services across the service delivery approaches. Composite FFIC scores were constructed and analyzed as the proportion of women who reported affirmatively to all elements and the mean score of positive responses. Satisfaction was assessed using a 4-point Likert scale. We used logistic regression to assess the association between the primary outcomes and mode of service delivery. RESULTS: In total, we interviewed 585 women (n=150 in Uganda, n=200 in Tanzania, and n=235 in the DRC). The large majority of clients in all countries and modalities received their method of choice. Clients of mobile outreach and special family planning days preferred LARCs and permanent methods, particularly implants, compared with clients at static services. Composite measures of FFIC were lower for mobile outreach than for static services in Tanzania among all family planning clients (odds ratio [OR]=0.5; P≤.001) and among LARC clients specifically (OR=0.5; P≤.01); no significant differences were found in the DRC or Uganda. A mean FFIC score among all family planning clients showed that clients in all modalities in all countries reported experiencing most elements of FFIC, with averages ranging from 4.8 to 6.1 of 7 elements. Among LARC clients specifically, mean scores ranged from 8.3 to 9.8 of 11 elements. Where greater proportions of clients experienced higher FFIC, greater proportions of clients also tended to report being "very satisfied" with aspects of services and counseling. CONCLUSIONS: The results underscore that special family planning days and mobile outreach services are important and viable ways to increase women's access to family planning services, notably to LARCs, but further attention to respecting and fulfilling clients' full, free, and informed choice across all service delivery modalities is required.

Safety of Tubal Occlusion by Minilaparotomy Provided by Trained Clinical Officers Versus Assistant Medical Officers in Tanzania: A Randomized, Controlled, Noninferiority Trial.

BACKGROUND: Tubal occlusion by minilaparotomy is a safe, highly effective, and permanent way to limit childbearing. We aimed to establish whether the safety of the procedure provided by trained clinical officers (COs) was not inferior to the safety when provided by trained assistant medical officers (AMOs), as measured by major adverse event (AE) rates. METHODS: In this randomized, controlled, open-label noninferiority trial, we enrolled participants at 7 health facilities in Arusha region, Tanzania, as well as during outreach activities conducted in Arusha and neighboring regions. Consenting, eligible participants were randomly allocated by a research assistant at each site to minilaparotomy performed by a trained CO or by a trained AMO, in a 1:1 ratio. We asked participants to return at 3, 7, and 42 days postsurgery. The primary outcome was the rate of major AEs following minilaparotomy performed by COs versus AMOs, during the procedure and through 42 days follow-up. The noninferiority margin was 2%. The trial is registered with ClinicalTrials.gov, Identifier NCT02944149. RESULTS: We randomly allocated 1,970 participants between December 2016 and June 2017, 984 to the CO group and 986 to the AMO group. Most (87%) minilaparotomies were conducted during outreach services. In the intent-to-treat analysis, 0 of 978 participants had a major AE in the CO group compared with 1 (0.1%) of 984 in the AMO group (risk difference: -0.1% [95% confidence interval: -0.3% to 0.1%]), meeting the criteria for noninferiority. We saw no evidence of differences in measures of procedure performance, participant satisfaction, or provider self-efficacy between the groups. CONCLUSIONS: Tubal occlusion by minilaparotomy performed by trained COs is safe, effective, and acceptable to women, and the procedure can be safely and effectively provided in outreach settings. Our results provide evidence to support policy change in resource-limited settings to allow task shifting of minilaparotomy to properly trained and supported COs, increasing access to female sterilization and helping to meet the rising demand for the procedure among women wanting to avoid pregnancy. They also suggest high demand for these services in Tanzania, given the large number of women recruited in a relatively short time period.

Safety of tubal ligation by minilaparotomy provided by clinical officers versus assistant medical officers: study protocol for a noninferiority randomized controlled trial in Tanzanian women.

BACKGROUND: Female sterilization by tubal ligation is a safe, extremely effective, and permanent way to limit childbearing. It is the most popular modern contraceptive method worldwide. The simplest way to provide tubal ligation is by a procedure called minilaparotomy, generally performed with the client under local anesthesia with systemic sedation and analgesia. In Tanzania, unmet need for family planning is high and has declined little in the past decade. Access to tubal ligation is limited throughout the country, in large part because of a lack of trained providers. Clinical officers (COs) are midlevel health workers who provide diagnosis, treatment, and minor surgeries. They are more prevalent than physicians in poorer and rural communities. Task shifting-the delegation of some tasks to less-specialized health workers, including task shifting of surgical procedures to midlevel cadres-has improved access to lifesaving interventions in resource-limited settings. It is a cost-effective way to address shortages of physicians, increasing access to services. The primary objective of this trial is to establish whether the safety of tubal ligation by minilaparotomy provided by COs is noninferior to the safety of tubal ligation by minilaparotomy provided by physicians (assistant medical officers [AMOs]), as measured by rates of major adverse events (AEs) during the procedure and through 42 days of follow-up. METHODS/DESIGN: In this facility-based, multicenter, noninferiority randomized controlled trial, we are comparing the safety of tubal ligation by minilaparotomy performed by trained COs versus by trained AMOs. The primary outcome is safety, defined by the overall rate of major AEs occurring during the minilaparotomy procedure and through 42 days of follow-up. The trial will be conducted among 1970 women 18 years of age or older presenting for tubal ligation at 7 study sites in northern Tanzania. DISCUSSION: If no major safety issues are identified, the data from this trial may facilitate changes in the Tanzanian government's regulations, allowing appropriately trained COs to provide tubal ligation by minilaparotomy. Positive findings may have broader implications. Task shifting to provide long-acting contraceptives, if proven safe, may be an effective approach to increasing contraceptive access in low- and middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02944149 . Registered on 14 October 2016.

Neonatal vaccination of low birthweight infants in Ghana.

OBJECTIVES: Global vaccination policy advocates for identifying and targeting groups who are underserved by vaccination to increase equity and uptake. We investigated whether birth weight and other factors are determinants of neonatal BCG vaccination in order to identify infants underserved by vaccination. METHODS: We used logistic regression to calculate adjusted ORs (AORs) for the association between birth weight (categorised as non-low birth weight (NLBW) (≥2.50 kg) and low birth weight (LBW) (2-2.49 kg, 1.50-1.99 kg and <1.50 kg)) and non-vaccination with BCG at the end of the neonatal period (0-27 days). We assessed whether this association varied by place of delivery and infant illness. We calculated how BCG timing and uptake would improve by ensuring the vaccination of all facility-born infants prior to discharge. RESULTS: There was a strong dose-response relationship between LBW and not receiving BCG in the neonatal period (p-trend<0.0001). Infants weighing 1.50-1.99 kg had odds of non-vaccination 1.6 times (AOR 1.64; 95% CI 1.30 to 2.08), and those weighing <1.50 kg 2.4 times (AOR 2.42; 95% CI 1.50 to 3.88) those of NLBW infants. Other determinants included place of delivery, distance to the health facility and socioeconomic status. Neither place of delivery nor infant illness modified the association between birth weight and vaccination (p-interaction all >0.19). Facility-born infants were vaccinated at a mean of 6 days, suggesting that they were not vaccinated in the facility at birth but were referred for vaccination. CONCLUSIONS: LBW is a risk factor for neonatal under-vaccination, even for facility-born infants. Ensuring vaccination at facility births would substantively improve timing and equitable BCG vaccination.

Development and validation of a simplified algorithm for neonatal gestational age assessment - protocol for the Alliance for Maternal Newborn Health Improvement (AMANHI) prospective cohort study.

OBJECTIVE: The objective of the Alliance for Maternal and Newborn Health Improvement (AMANHI) gestational age study is to develop and validate a programmatically feasible and simple approach to accurately assess gestational age of babies after they are born. The study will provide accurate, population-based rates of preterm birth in different settings and quantify the risks of neonatal mortality and morbidity by gestational age and birth weight in five South Asian and sub-Saharan African sites. METHODS: This study used on-going population-based cohort studies to recruit pregnant women early in pregnancy (<20 weeks) for a dating ultrasound scan. Implementation is harmonised across sites in Ghana, Tanzania, Zambia, Bangladesh and Pakistan with uniform protocols and standard operating procedures. Women whose pregnancies are confirmed to be between 8 to 19 completed weeks of gestation are enrolled into the study. These women are followed up to collect socio-demographic and morbidity data during the pregnancy. When they deliver, trained research assistants visit women within 72 hours to assess the baby for gestational maturity. They assess for neuromuscular and physical characteristics selected from the Ballard and Dubowitz maturation assessment scales. They also measure newborn anthropometry and assess feeding maturity of the babies. Computer machine learning techniques will be used to identify the most parsimonious group of signs that correctly predict gestational age compared to the early ultrasound date (the gold standard). This gestational age will be used to categorize babies into term, late preterm and early preterm groups. Further, the ultrasound-based gestational age will be used to calculate population-based rates of preterm birth. IMPORTANCE OF THE STUDY: The AMANHI gestational age study will make substantial contribution to improve identification of preterm babies by frontline health workers in low- and middle- income countries using simple evaluations. The study will provide accurate preterm birth estimates. This new information will be crucial to planning and delivery of interventions for improving preterm birth outcomes, particularly in South Asia and sub-Saharan Africa.

5-HT(2C) receptor RNA editing in the amygdala of C57BL/6J, DBA/2J, and BALB/cJ mice.

Post-transcriptional RNA editing of the G-protein coupled 5-hydroxytryptamine-2C (5-HT(2C)) receptor predicts an array of 24 receptor isoforms, some of which are characterized by reduced constitutive activity and potency to initiate intracellular signaling. The amygdala is integral to anxiety, fear, and related psychiatric diseases. Activation of 5-HT(2C) receptors within the amygdala is anxiogenic. Here, we describe the RNA editing profiles from amygdala of two inbred mouse strains (BALB/cJ and DBA/2J) known to be more anxious than a third (C57BL/6J). We confirmed the strain anxiety differences using light<-->dark exploration, and we discovered that BALB/cJ and DBA/2J are each characterized by a higher functioning RNA editing profile than C57BL/6J. BALB/cJ and DBA/2J exhibit a roughly two-fold reduction in C site editing, and a corresponding two-fold reduction in the edited isoform VSV. C57BL/6J is characterized by a relative decrease in the unedited highly functional isoform INI. We estimated the heritability of editing at the C site to be approximately 40%. By sequencing genomic DNA, we found complete conservation between C57BL/6J, BALB/cJ, DBA/2J and 37 other inbred strains for the RNA edited region of Htr2c, suggesting Htr2c DNA sequence does not influence variation in Htr2c RNA editing between inbred strains of mice. We did, however, discover that serotonin turnover is reduced in BALB/cJ and DBA/2J, consistent with emerging evidence that synaptic serotonin levels regulate RNA editing. These results encourage further study of the causes and consequences of 5-HT(2C) receptor RNA editing in the amygdala of mice.

Health service provider education and/or training in infant male circumcision to improve short- and long-term morbidity outcomes: protocol for systematic review.

BACKGROUND: There has been an expansion of circumcision services in Africa as part of a long-term HIV prevention strategy. However, the effect of infant male circumcision on morbidity and mortality still remains unclear. Acute morbidities associated with circumcision include pain, bleeding, swelling, infection, tetanus or inadequate skin removal. Scale-up of circumcision services could lead to a rise in these associated morbidities that could have significant impact on health service delivery and the safety of infants. Multidisciplinary training programmes have been developed to improve skills of health service providers, but very little is known about the effectiveness of health service provider education and/or training for infant male circumcision on short- and long-term morbidity outcomes. This review aims to evaluate the effectiveness of health service provider education and/or training for infant male circumcision on short- and long-term morbidity outcomes. METHODS/DESIGN: The review will include studies comparing health service providers who have received education and/or training to improve their skills for infant male circumcision with those who have not received education and/or training. Randomised controlled trials (RCTs) and cluster RCTs will be included. The outcomes of interest are short-term morbidities of the male infant including pain, infection, tetanus, bleeding, excess skin removal, glans amputation and fistula. Long-term morbidities include urinary tract infection (UTI), HIV infection and abnormalities of urination. Databases such as MEDLINE (OVID), PsycINFO (OVID), EMBASE (OVID), CINAHL, Cochrane Library (including CENTRAL and DARE), WHO databases and reference list of papers will be searched for relevant articles. Study selection, data extraction and synthesis and risk of bias assessment using the Cochrane risk of bias assessment tool will be conducted. We will calculate the pooled estimates of the difference in means and risk ratios using random effects models. If insufficient data are available, we will present results descriptively. DISCUSSION: This review appears to be the first to be conducted in this area. The findings will have important implications for infant male circumcision programmes and policy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015029345.

Vaginal and Rectal Clostridium sordellii and Clostridium perfringens Presence Among Women in the United States.

OBJECTIVE: To characterize the presence of Clostridium sordellii and Clostridium perfringens in the vagina and rectum, identify correlates of presence, and describe strain diversity and presence of key toxins. METHODS: We conducted an observational cohort study in which we screened a diverse cohort of reproductive-aged women in the United States up to three times using vaginal and rectal swabs analyzed by molecular and culture methods. We used multivariate regression models to explore predictors of presence. Strains were characterized by pulsed-field gel electrophoresis and tested for known virulence factors by polymerase chain reaction assays. RESULTS: Of 4,152 participants enrolled between 2010 and 2013, 3.4% (95% confidence interval [CI] 2.9-4.0) were positive for C sordellii and 10.4% (95% CI 9.5-11.3) were positive for C perfringens at baseline. Among the 66% with follow-up data, 94.7% (95% CI 88.0-98.3) of those positive for C sordellii and 74.4% (95% CI 69.0-79.3) of those positive for C perfringens at baseline were negative at follow-up. At baseline, recent gynecologic surgery was associated with C sordellii presence, whereas a high body mass index was associated with C perfringens presence in adjusted models. Two of 238 C sordellii isolates contained the lethal toxin gene, and none contained the hemorrhagic toxin gene. Substantial strain diversity was observed in both species with few clusters and no dominant clones identified. CONCLUSION: The relatively rare and transient nature of C sordellii and C perfringens presence in the vagina and rectum makes it inadvisable to use any screening or prophylactic approach to try to prevent clostridial infection. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01283828.

Multicenter trial of a simplified mifepristone medical abortion regimen.

OBJECTIVE: To provide evidence regarding the safety, efficacy, and acceptability of 200 mg mifepristone followed by home administration of 400 mug oral misoprostol METHODS: The 376 women enrolled in this prospective, open-label, multicenter trial were administered mifepristone in the clinic and were given 2 tablets of 200 mug misoprostol to swallow at home 48 hours later. On day 15, women returned to the clinic for a gynecologic examination. Success was defined as a complete termination without surgical intervention or additional misoprostol by day 21. All participants completed an exit interview before discharge from the study RESULTS: Of the women enrolled, 58.8% had gestations of between 43 and 49 days, 54.7% had had a previous abortion, and 76% had had a previous pregnancy. Of the 354 women included in the efficacy analysis, 324 (91.5%) had a successful termination. The most common adverse effects reported by patients were pain or cramps (93.2%) and nausea (66.6%), followed by weakness (54.7%), headache (46.2%), and dizziness (44.4%). Overall acceptability of the regimen was high, with 63.3% of women reporting that it was very satisfactory and an additional 23% reporting that it was satisfactory CONCLUSION: A regimen of 200 mg mifepristone followed in 48 hours by home administration of 400 mug oral misoprostol is effective, associated with rare severe adverse effects or adverse events, and acceptable for women seeking medical abortion of pregnancies of up to 49 days duration as compared with the regimen currently approved by the Food and Drug Administration. LEVEL OF EVIDENCE: III.

Randomized trial of mifepristone and buccal or vaginal misoprostol for abortion through 56 days of last menstrual period.

OBJECTIVE: Mifepristone-misoprostol medical abortion has been approved in the United States since 2000. U.S. providers have preferred to use vaginal misoprostol because of evidence that such a regimen is more effective in later gestations. Buccal administration of misoprostol may be equally effective and more acceptable to some women. METHODS: This open-label, randomized trial was conducted at two sites in Rochester, NY, and involved healthy women with pregnancies through 56 days since the last menstrual period (LMP) as indicated by sonogram. Women received mifepristone 200 mg orally and were randomized to use 800 mug of misoprostol either buccally or vaginally 1 to 2 days later. They returned within 15 days for repeat sonogram. If the woman's pregnancy had not been completely aborted by day 36, a suction abortion was performed. The primary outcome was a complete abortion without surgical intervention. RESULTS: Four hundred forty-two women were enrolled in the study, and complete data were available on 429. The efficacy rate was 95% (205/216) in the buccal group and 93% (199/213) in the vaginal group (chi(2)=0.43, p=.51). Nausea was the most commonly reported side effect, affecting 70% in the buccal group and 62% in the vaginal group. There were no differences in the satisfaction with the overall procedure between the buccal (92%) and the vaginal groups (95%) (chi(2)=1.87, p=.17). CONCLUSION: Buccal administration of misoprostol after low-dose mifepristone for medical abortion appears to be a highly effective and acceptable alternative compared with vaginal administration for medical abortion in pregnancies through 56 days LMP.

A fatal case of Clostridium sordellii septic shock syndrome associated with medical abortion.

BACKGROUND: Clostridia bacteria are infrequent human pathogens. In the obstetric and gynecologic literature, Clostridium sordellii infections have been very rarely reported. This is a case of infection following medical termination of early pregnancy with mifepristone and misoprostol. CASE: A 27-year-old woman presented for termination of pregnancy at 5.5 weeks from her last menstrual period. She received mifepristone 200 mg orally followed by 800 microg vaginal misoprostol. Three days after administration of misoprostol, she complained of dizziness, pelvic pain, and bleeding. The next day, she experienced worsening of symptoms and was hospitalized. She developed pulmonary edema, ascites, and heart failure. Despite supportive measures, antibiotics, and hysterectomy, she died 3 days later. The post mortem examinations indicated that death was caused by shock secondary to C sordellii infection. CONCLUSION: The frequency of infection following medical abortion is low. The rapid and fatal course of this infection is similar to other obstetric and gynecologic cases reported in the literature. Although providers should remain vigilant to the possibility of infection following medical abortion, the overall proven safety of medical abortion remains the same.

Ectopic pregnancy and medical abortion.

OBJECTIVE: Medical abortion regimens have become more widely used to terminate early pregnancies. Medical abortion providers are concerned to diagnose and exclude women with ectopic pregnancy before initiating treatment, as with any early pregnancy termination. Yet, there is little information about whether the various pretreatment screening methods used are adequate. We reviewed published literature to determine the overall success of screening for ectopic pregnancy before medical abortion treatment. DATA SOURCES: We searched MEDLINE for articles on medical abortion regimens published before July 2003. METHODS OF STUDY SELECTION: We selected English language articles of studies of medical abortion with sample sizes greater than 100, which reported on ectopic pregnancy diagnosed after medical abortion treatment. Fifty-seven of 85 prospective studies and randomized trials (69%) met these inclusion criteria. We also included data from 2 unpublished studies because they were large and well-controlled and because they included serious adverse events known to us, which we did not deem fair to exclude from our analysis. TABULATION, INTEGRATION, AND RESULTS: Each article was reviewed by one author. Data from selected studies were compiled, and the frequency of ectopic pregnancy diagnosed after medical abortion treatment was calculated. Ectopic pregnancy was diagnosed very infrequently following medical abortion procedures, occurring in only 10 of 44,789 (0.02%) women. CONCLUSION: The very low frequency of ectopic pregnancies diagnosed after medical abortion treatment demonstrates that the various pretreatment screening methods that providers use to exclude patients with ectopic pregnancies are successful. Further, there is no evidence to suggest that medical abortion treatment leads to unusual complications for women with ectopic pregnancies.

Misoprostol for women's health: a review.

OBJECTIVE: To review published literature on misoprostol for women's health indications to provide a synthesis of available information and highlight areas in need of additional research. DATA SOURCES: Studies were identified through searches of medical literature databases including MEDLINE, Cochrane Database, and Popline, in addition to a review of references from identified articles. STUDY SELECTION: We included all studies reported in English and published before March 31, 2001, which evaluated the efficacy of misoprostol alone for labor and delivery, evacuation of the uterus after pregnancy failure and induced abortion. Studies were not excluded based on quality or sample size. TABULATION, INTEGRATION, AND RESULTS: Misoprostol shows promise for all of the women's health indications addressed. Currently available data, though, are often hard to interpret because of variations in regimen, dose, and outcome measures. The low cost, ease of administration and storage, and widespread availability of misoprostol make it particularly appealing for developing countries. Because many of the women's health problems for which misoprostol could be prescribed currently cause significant mortality and morbidity, increased access to and information on use of misoprostol could help improve women's health especially where these problems are most severe. CONCLUSION: Further research is needed to identify optimal regimens for misoprostol for obstetric and gynecologic health indications. Registering misoprostol with national drug regulatory authorities for any of several women's health indications could help increase access to and safe use of this drug. Provider training would be a logical subsequent step.