A Randomized Trial of Prophylactic Antibiotics for Miscarriage Surgery.

BACKGROUND: Surgical intervention is needed in some cases of spontaneous abortion to remove retained products of conception. Antibiotic prophylaxis may reduce the risk of pelvic infection, which is an important complication of this surgery, particularly in low-resource countries. METHODS: We conducted a double-blind, placebo-controlled, randomized trial investigating whether antibiotic prophylaxis before surgery to complete a spontaneous abortion would reduce pelvic infection among women and adolescents in low-resource countries. We randomly assigned patients to a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole or identical placebos. The primary outcome was pelvic infection within 14 days after surgery. Pelvic infection was defined by the presence of two or more of four clinical features (purulent vaginal discharge, pyrexia, uterine tenderness, and leukocytosis) or by the presence of one of these features and the clinically identified need to administer antibiotics. The definition of pelvic infection was changed before the unblinding of the data; the original strict definition was two or more of the clinical features, without reference to the administration of antibiotics. RESULTS: We enrolled 3412 patients in Malawi, Pakistan, Tanzania, and Uganda. A total of 1705 patients were assigned to receive antibiotics and 1707 to receive placebo. The risk of pelvic infection was 4.1% (68 of 1676 pregnancies) in the antibiotics group and 5.3% (90 of 1684 pregnancies) in the placebo group (risk ratio, 0.77; 95% confidence interval [CI], 0.56 to 1.04; P = 0.09). Pelvic infection according to original strict criteria was diagnosed in 1.5% (26 of 1700 pregnancies) and 2.6% (44 of 1704 pregnancies), respectively (risk ratio, 0.60; 95% CI, 0.37 to 0.96). There were no significant between-group differences in adverse events. CONCLUSIONS: Antibiotic prophylaxis before miscarriage surgery did not result in a significantly lower risk of pelvic infection, as defined by pragmatic broad criteria, than placebo. (Funded by the Medical Research Council and others; AIMS Current Controlled Trials number, ISRCTN97143849.).

Analysis of maternal serum vitamin D concentrations at birth in women presenting with spontaneous preterm birth: A case-control study.

Vitamin D is a potent immune system modulator; its deficiency correlates with increased susceptibility to infections. We evaluated the status of maternal serum vitamin D in women with spontaneous preterm birth. In this case-control study, the maternal serum concentration of vitamin D (25OH D) was measured in 95 women delivering preterm and 92 women having a term birth. Vitamin D sufficiency was found in 79% of the mothers who delivered preterm and 80.4% of the mothers who had term birth (p=0.822). There was a negative correlation between maternal serum concentration of 25 Hydroxyvitamin D and maternal age in the preterm birth group (p=0.043). In conclusion, there was no difference in maternal serum concentrations of 25 Hydroxyvitamin D between women delivering preterm compared to those having term birth. Maternal serum concentration of 25 Hydroxyvitamin D is not associated with occurrence of preterm birth.

Qualitative assessment of attitudes and knowledge on preterm birth in Malawi and within country framework of care.

BACKGROUND: The overarching goal of this study was to qualitatively assess baseline knowledge and perceptions regarding preterm birth (PTB) and oral health in an at-risk, low resource setting surrounding Lilongwe, Malawi. The aims were to determine what is understood regarding normal length of gestation and how gestational age is estimated, to identify common language for preterm birth, and to assess what is understood as options for PTB management. As prior qualitative research had largely focused on patient or client-based focused groups, we primarily focused on groups comprised of community health workers (CHWs) and providers. METHODS: A qualitative study using focus-group discussions, incidence narrative, and informant interviews amongst voluntary participants. Six focus groups were comprised of CHWs, patient couples, midwives, and clinical officers (n = 33) at two rural health centers referring to Kamuzu Central Hospital. Semi-structured questions facilitated discussion of PTB and oral health (inclusive of periodontal disease), including definitions, perception, causation, management, and accepted interventions. RESULTS: Every participant knew of women who had experienced "a baby born too soon", or preterm birth. All participants recognized both an etiology conceptualization and disease framework for preterm birth, distinguished PTB from miscarriage and macerated stillbirth, and articulated a willingness to engage in studies aimed at prevention or management. Identified gaps included: (1) discordance in the definition of PTB (i.e., 28-34 weeks or less than the 8th month, but with a corresponding fetal weight ranging 500 to 2300 grams); (2) utility and regional availability of antenatal steroids for prevention of preterm infant morbidity and mortality; (3) need for antenatal referral for at-risk women, or with symptoms of preterm birth. There was no evident preference for route of progesterone for the prevention of recurrent PTB. CONCLUSIONS: Qualitative research was useful in (1) identifying gaps in knowledge in urban and rural Malawi, and (2) informing the development of educational materials and implementation of programs or trials ultimately aimed at reducing PTB. As a result of this qualitative work, implementation planning was focused on the gaps in knowledge, dissemination of knowledge (to both patients and providers), and practical solutions to barriers in known efficacious therapies.

Effectiveness of a training intervention in increasing the use of misoprostol in postabortion care in Malawi: a quasi-experimental study.

OBJECTIVES: The study was conducted to determine effectiveness of a training intervention in increasing use of misoprostol in management of incomplete abortions. DESIGN: A quasi-experimental study with training intervention on use of misoprostol in treatment of incomplete abortion. SETTING: Five secondary-level public hospitals in Malawi, one in urban and four in semiurban settings. Three intervention and two control sites. PARTICIPANTS: Records of women treated for first-trimester incomplete abortion from March to May 2020 (baseline) and April to June 2021 (endline). Clinical data were collected from 865 records, 421 before and 444 after the intervention in all study sites. INTERVENTION: Three-hour theoretical training sessions for 81 healthcare workers were conducted in July 2020 at the three intervention sites. PRIMARY AND SECONDARY OUTCOME MEASURES: Proportion of women with incomplete abortion treated with misoprostol before and after the intervention. The proportion of women treated with sharp curettage at the study sites. RESULTS: At the intervention sites, there was a significant increase in use of misoprostol from 22.8% (95% CI 17.9% to 28.0%) to 35.9% (95% CI 30.5% to 41.6%) and significant reduction in use of sharp curettage from 48.1% (95% CI 41.9% to 54.3%) to 39.4% (95% CI 35.3% to 42.6%) p<0.01 at baseline and endline, respectively. The use of misoprostol was significantly higher at the intervention sites with OR of 5.02 (95% CI 1.7 to 14.7) p<0.05 compared with control sites at the endline in multivariable models, and there was a difference in the difference of 14.4% ((95% CI 10.4% to 18.2%) p<0.001) between the intervention and control sites after the intervention. CONCLUSIONS: A training intervention effectively increased the use of misoprostol in the treatment of incomplete abortions. Increasing misoprostol use will make treatment of incomplete abortion cheaper, easier and more easily accessible. Making quality postabortion care accessible to more women may reduce maternal morbidity and mortality. Further training interventions are recommended.

Experiences of Using Misoprostol in the Management of Incomplete Abortions: A Voice of Healthcare Workers in Central Malawi.

Complications after abortion are a major cause of maternal death. Incomplete abortions are common and require treatment with surgical or medical uterine evacuation. Even though misoprostol is a cheaper and safer option, it is rarely used in Malawi. To improve services, an intervention was performed to increase the use of misoprostol in post-abortion care. This study explored healthcare providers' perceptions and experiences with misoprostol in the Malawian setting and their role in achieving effective implementation of the drug. A descriptive phenomenological study was conducted in three hospitals in central Malawi. Focus group discussions were conducted with healthcare workers in centres where the training intervention was offered. Participants were purposefully sampled, and thematic analysis was done. Most of the healthcare workers were positive about the use of misoprostol, knew how to use it and were confident in doing so. The staff preferred misoprostol to surgical treatment because it was perceived safe, effective, easy to use, cost-effective, had few complications, decreased hospital congestion, reduced workload, and saved time. Additionally, misoprostol was administered by nurses/midwives, and not just physicians, thus enhancing task-shifting. The results showed acceptability of misoprostol in post-abortion care among healthcare workers in central Malawi, and further implementation of the drug is recommended.

Estimation of potential effects of improved community-based drug provision, to augment health-facility strengthening, on maternal mortality due to post-partum haemorrhage and sepsis in sub-Saharan Africa: an equity-effectiveness model.

BACKGROUND: Maternal mortality in Africa has changed little since 1990. We developed a mathematical model with the aim to assess whether improved community-based access to life-saving drugs, to augment a core programme of health-facility strengthening, could reduce maternal mortality due to post-partum haemorrhage or sepsis. METHODS: We developed a mathematical model by considering the key events leading to maternal death from post-partum haemorrhage or sepsis after delivery. With parameter estimates from published work of occurrence of post-partum haemorrhage and sepsis, case fatality, and the effectiveness of drugs, we used this model to estimate the effect of three potential packages of interventions: 1) health-facility strengthening; 2) health-facility strengthening combined with improved drug provision via antenatal-care appointments and community health workers; and 3) all interventions in package two combined with improved community-based drug provision via female volunteers in villages. The model was applied to Malawi and sub-Saharan Africa. FINDINGS: In the implementation of the model, the lowest risk deliveries were those in health facilities. With the model we estimated that of 2860 maternal deaths from post-partum haemorrhage or sepsis per year in Malawi, intervention package one could prevent 210 (7%) deaths, package two 720 (25%) deaths, and package three 1020 (36%) deaths. In sub-Saharan Africa, we estimated that of 182 000 of such maternal deaths per year, these three packages could prevent 21 300 (12%), 43 800 (24%), and 59 000 (32%) deaths, respectively. The estimated effect of community-based drug provision was greatest for the poorest women. INTERPRETATION: Community provision of misoprostol and antibiotics to reduce maternal deaths from post-partum haemorrhage and sepsis could be a highly effective addition to health-facility strengthening in Africa. Investigation of such interventions is urgently needed to establish the risks, benefits, and challenges of widespread implementation. FUNDING: Institute of Child Health and Faculty of Mathematical and Physical Sciences, University College London, and a donation from John and Ann-Margaret Walton.

Maternal Serum Concentrations of Selenium, Copper, and Zinc during Pregnancy Are Associated with Risk of Spontaneous Preterm Birth: A Case-Control Study from Malawi.

Preterm birth is delivery before 37 completed weeks. A study was conducted to evaluate the association of maternal serum concentrations of selenium, copper, and zinc and preterm birth. There were 181 women in this nested case-control study, 90/181 (49.7%) term and 91/181 (50.3%) preterm pregnant women. The overall mean serum concentration of selenium was 77.0, SD 19.4 µg/L; of copper was 2.50, SD 0.52 mg/L; and of zinc was 0.77, SD 0.20 mg/L with reference values of 47-142 µg/L, 0.76-1.59 mg/L, and 0.59-1.11 mg/L, respectively. For preterm birth, mean serum concentration for selenium was 79.7, SD 21.6 µg/L; for copper was 2.61, SD 0.57 mg/L; and for zinc was 0.81, SD 0.20 mg/L compared to that for term births: selenium (74.2; SD 16.5 µg/L; p = 0.058), copper (2.39; SD 0.43 mg/L; p = 0.004), and zinc (0.73; SD 0.19 mg/L; p = 0.006), respectively. In an adjusted analysis, every unit increase in maternal selenium concentrations gave increased odds of being a case OR 1.01 (95% CI: 0.99; 1.03), p = 0.234; copper OR 1.62 (95% CI: 0.80; 3.32), p = 0.184; zinc OR 6.88 (95% CI: 1.25; 43.67), p = 0.032. Results show that there was no deficiency of selenium and zinc and there were high serum concentrations of copper in pregnancy. Preterm birth was associated with higher maternal serum concentrations of copper and zinc.

Population-Based Estimation of the Preterm Birth Rate in Lilongwe, Malawi: Making Every Birth Count.

Objective The objective of this study was to perform a population-based estimation of the preterm birth (PTB) rate in regions surrounding Lilongwe, Malawi. Study Design We partnered with obstetrician specialists, community health workers, local midwives, and clinicians in a 50 km region surrounding Lilongwe, Malawi, to perform a population-based estimation of the PTB rate during the study period from December 1, 2012 to May 19, 2015. Results Of the 14,792 births captured, 19.3% of births were preterm, including preterm early neonatal deaths. Additional PTB risk factors were similarly prevalent including domestic violence, HIV, malaria, anemia, and malnutrition. Conclusion When performing a population-based estimation of the rate of PTB, including women without antenatal care and women delivering at home, the 19.3% rate of PTB is among the highest recorded globally. This is accompanied by a high rate of risk factors and comorbid conditions.

Qualitative assessment of knowledge transfer regarding preterm birth in Malawi following the implementation of targeted health messages over 3 years.

BACKGROUND: In 2012, we performed a needs assessment and gap analysis to qualitatively assess providers' and patients' knowledge and perceptions regarding preterm birth (PTB). During the study, we identified knowledge gaps surrounding methods to reduce the risk of occurrence of PTB and management options if preterm labor/birth occur. We targeted health messages toward these gaps. The objective of the present study was to assess the impact of our community health worker-based patient education program 3 years after it was implemented. METHODS: Fifteen focus groups including 70 participants were included in the study. The groups comprised either patients/patient couples or health providers. A minimum of two facilitators led each group using 22 a priori designed and standardized lead-in prompts for participants with four additional prompts for providers only. A single researcher recorded responses, and transcript notes were reviewed by the facilitators and interpreters immediately following each group discussion to ensure accuracy. RESULTS: The understanding of term vs preterm gestation was generally accurate. Every participant knew of women who had experienced PTB, and the general perception was that two to three women out of every ten had this experience. The majority of respondents thought that women should present to their local health clinic if they experience preterm contractions; few were aware of the use of antenatal steroids for promoting fetal lung maturity, but many acknowledged that the neonate may be able to receive life-sustaining treatment if born at a higher level of care facility. The majority of participants were aware that PTB could recur in subsequent pregnancies. All respondents were able to list ways that women could potentially reduce the risk of PTB. CONCLUSION: After employing targeted health messages, the majority of participants expressed improved understanding of the definition of PTB, methods to prevent risk of PTB, and management options for preterm labor or PTB.

Population-Based Estimation of Dental Caries and Periodontal Disease Rates of Gravid and Recently Postpartum Women in Lilongwe, Malawi.

Objectives The objective of this study was to determine the rate of dental caries and periodontal disease among gravid and recently postpartum women at five delivery centers within and surrounding Lilongwe, Malawi. Study Design We partnered with obstetric specialists, community health workers, and dentists to perform dental history interviews and dental examinations during the study period from December 2012 to May 2014. Dental examinations were performed according to World Health Organization standards to assess periodontal and oral health status. Results Among the 387 gravid and recently postpartum women, the rate of dental caries was 69.3% and the rate of composite dental disease (caries and periodontal disease) was 76.7%. The majority (69.5%) of women examined had a decayed-missing-filled (DMF) index greater than or equal to one; the average DMF Index was 2.48. The majority of women had never seen a dentist (62.8%). However, most did perform oral hygiene, two or more times per day (90.2%); most women reported brushing with toothpaste (88.1%). Conclusion When assessing this population for dental caries and periodontal disease, the rate of dental disease was high. Therefore, this may be an ideal setting to test for impactful interventions aimed at reducing caries and periodontal disease.

A tailored approach to building specialized surgical oncology capacity: Early experiences and outcomes in Malawi.

OBJECTIVES: Cervical cancer can often be cured by surgery alone, if diagnosed and treated early. However, of the cancer patients who live in the world's poorest countries less that 5% have access to safe, effective and timely cancer surgery. We designed a novel, competency-based curriculum to rapidly build surgical capacity for the treatment of cervical cancer. Here we report experiences and early outcomes of its implementation in Malawi. METHODS: Curriculum implementation consisted of preoperative evaluation of patients and surgical video review, discussion of surgical instruments and suture material, deconstruction of the surgical procedure into critical subcomponents including trainees walking through the steps of the procedure with the master trainers, high-volume surgical repetition over a short time interval, intra-operative mentoring, post-operative case review, and mental narration. This was preceded by self-directed learning and followed by clinical mentorship through electronic communication and quarterly on-site visits. RESULTS: Between June 2015-June 2017, 28 patients underwent radical abdominal hysterectomy with bilateral pelvic lymphadenectomy. The first 8 surgeries were performed over 5 days. After the 7th case the trainee could perform the procedure alone. During and between quarterly mentoring-visits the trainee independently performed the procedure on 20 additional patients. Major surgical complications were rare. CONCLUSIONS: Life-saving surgical treatment for cervical cancer is now available for the first time, as a routine clinical service, in Central/Northern, Malawi.

Prophylactic antibiotics to reduce pelvic infection in women having miscarriage surgery - The AIMS (Antibiotics in Miscarriage Surgery) trial: study protocol for a randomized controlled trial.

BACKGROUND: The estimated annual global burden of miscarriage is 33 million out of 210 million pregnancies. Many women undergoing miscarriage have surgery to remove pregnancy tissues, resulting in miscarriage surgery being one of the most common operations performed in hospitals in low-income countries. Infection is a serious consequence and can result in serious illness and death. In low-income settings, the infection rate following miscarriage surgery has been reported to be high. Good quality evidence on the use of prophylactic antibiotics for surgical miscarriage management is not available. Given that miscarriage surgery is common, and infective complications are frequent and serious, prophylactic antibiotics may offer a simple and affordable intervention to improve outcomes. METHODS: Eligible patients will be approached once the diagnosis of miscarriage has been made according to local practice. Once informed consent has been given, participants will be randomly allocated using a secure internet facility (1:1 ratio) to a single dose of oral doxycycline (400 mg) and metronidazole (400 mg) or placebo. Allocation will be concealed to both the patient and the healthcare providers. A total of 3400 women will be randomised, 1700 in each arm. The medication will be given approximately 2 hours before surgery, which will be provided according to local practice. The primary outcome is pelvic infection 2 weeks after surgery. Women will be invited to the hospital for a clinical assessment at 2 weeks. Secondary outcomes include overall antibiotic use, individual components of the primary outcome, death, hospital admission, unplanned consultations, blood transfusion, vomiting, diarrhoea, adverse events, anaphylaxis and allergy, duration of clinical symptoms, and days before return to usual activities. An economic evaluation will be performed to determine if prophylactic antibiotics are cost-effective. DISCUSSION: This trial will assess whether a single dose of doxycycline (400 mg) and metronidazole (400 mg) taken orally 2 hours before miscarriage surgery can reduce the incidence of pelvic infection in women up to 2 weeks after miscarriage surgery. TRIAL REGISTRATION: Registered with the ISRCTN (international standard randomised controlled trial number) registry: ISRCTN 97143849 . (Registered on April 17, 2013).

High rates of cervical cancer among HIV-infected women at a referral hospital in Malawi.

Cervical cancer is the most common cancer among women in Malawi. National guidelines recommend screening women aged 30-45 years every five years; however, no specific recommendations exist for women with HIV. We aimed to assess the frequency of high-grade dysplasia (CIN 2 or CIN3) and cervical cancer among women in central Malawi and to examine associations with CIN2+ (CIN2/3 or cancer). We extracted cervical Pap smear, biopsy, loop electrosurgical excision procedure and uterine specimen reports from a hospital pathology database from November 2012 to November 2013. We used logistic regression to estimate associations with CIN2+. We reviewed specimens from 824 women; we excluded 194 with unknown HIV status, leaving 630 in the analytic sample. Twelve percent had high-grade dysplasia and 109 women (17%) had cancer. Twenty-five percent of high-grade dysplasia cases and 35% of cancers occurred among women outside recommended screening ages. The odds of having CIN2+ were 6.55 times (95% CI 4.44-9.67) greater for HIV+ women. High-grade dysplasia and cervical cancer are very common among Malawian women, especially HIV+ women. HIV infection was strongly associated with CIN2+. Expanding screening to women not covered by current guidelines could avert a substantial proportion of cervical cancer cases in Malawi.

Evaluating nurses' implementation of an infant-feeding counseling protocol for HIV-infected mothers: The Ban Study in Lilongwe, Malawi.

A process evaluation of nurses' implementation of an infant-feeding counseling protocol was conducted for the Breastfeeding, Antiretroviral and Nutrition (BAN) Study, a prevention of mother-to-child transmission of HIV clinical trial in Lilongwe, Malawi. Six trained nurses counseled HIV-infected mothers to exclusively breastfeed for 24 weeks postpartum and to stop breastfeeding within an additional four weeks. Implementation data were collected via direct observations of 123 infant feeding counseling sessions (30 antenatal and 93 postnatal) and interviews with each nurse. Analysis included calculating a percent adherence to checklists and conducting a content analysis for the observation and interview data. Nurses were implementing the protocol at an average adherence level of 90% or above. Although not detailed in the protocol, nurses appropriately counseled mothers on their actual or intended formula milk usage after weaning. Results indicate that nurses implemented the protocol as designed. Results will help to interpret the BAN Study's outcomes.