Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis.

BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

Development and Pilot Test of a Multi-Component Intervention to Support Women's Recovery from Female Genital Fistula.

INTRODUCTION AND HYPOTHESIS: We evaluated a pilot multi-component reintegration intervention to improve women's physical and psychosocial quality of life after genital fistula surgery. METHODS: Twelve women undergoing fistula repair at Mulago Specialized Women and Neonatal Hospital (Kampala, Uganda) anticipated in a 2-week multi-component intervention including health education, psychosocial therapy, physiotherapy, and economic investment. We assessed feasibility through recruitment, retention, and adherence, acceptability through intervention satisfaction, and preliminary effectiveness through reintegration, mental health, physical health, and economic status. We collected quantitative data at enrollment, 6 weeks, 3 months, and 6 months. We conducted in-depth interviews with six participants. Quantitative data are presented descriptively, and qualitative data analyzed thematically. RESULTS: Participants had a median age of 34.5 years (25.5-38.0), 50% were married/partnered, 42% were separated, 50$ had completed less than primary education, and 67% were unemployed. Mean number of sessions received was 12 for health education (range 5-15), 8 for counseling (range 8-9), and 6 for physiotherapy (range 4-8). Feasibility was demonstrated by study acceptance among all those eligible (100%); comfort with study measures, data collection frequency and approach; and procedural fidelity. Acceptability was high; all participants reported being very satisfied with the intervention and each of the components. Participant narratives echoed quantitative findings and contributed nuanced perspectives to understanding approach and content. CONCLUSIONS: Our results suggest that the intervention and associated research were both feasible and acceptable, and suggested certain modifications to the intervention protocol to reduce participant burden. Further research to determine the effectiveness of the intervention above and beyond surgery alone with regard to the health and well-being of women with fistulas is warranted.

A Randomized Trial of Laryngeal Mask Airway in Neonatal Resuscitation.

BACKGROUND: Face-mask ventilation is the most common resuscitation method for birth asphyxia. Ventilation with a cuffless laryngeal mask airway (LMA) has potential advantages over face-mask ventilation during neonatal resuscitation in low-income countries, but whether the use of an LMA reduces mortality and morbidity among neonates with asphyxia is unknown. METHODS: In this phase 3, open-label, superiority trial in Uganda, we randomly assigned neonates who required positive-pressure ventilation to be treated by a midwife with an LMA or with face-mask ventilation. All the neonates had an estimated gestational age of at least 34 weeks, an estimated birth weight of at least 2000 g, or both. The primary outcome was a composite of death within 7 days or admission to the neonatal intensive care unit (NICU) with moderate-to-severe hypoxic-ischemic encephalopathy at day 1 to 5 during hospitalization. RESULTS: Complete follow-up data were available for 99.2% of the neonates. A primary outcome event occurred in 154 of 563 neonates (27.4%) in the LMA group and 144 of 591 (24.4%) in the face-mask group (adjusted relative risk, 1.16; 95% confidence interval [CI], 0.90 to 1.51; P = 0.26). Death within 7 days occurred in 21.7% of the neonates in the LMA group and 18.4% of those in the face-mask group (adjusted relative risk, 1.21; 95% CI, 0.90 to 1.63), and admission to the NICU with moderate-to-severe hypoxic-ischemic encephalopathy at day 1 to 5 during hospitalization occurred in 11.2% and 10.1%, respectively (adjusted relative risk, 1.27; 95% CI, 0.84 to 1.93). Findings were materially unchanged in a sensitivity analysis in which neonates with missing data were counted as having had a primary outcome event in the LMA group and as not having had such an event in the face-mask group. The frequency of predefined intervention-related adverse events was similar in the two groups. CONCLUSIONS: In neonates with asphyxia, the LMA was safe in the hands of midwives but was not superior to face-mask ventilation with respect to early neonatal death and moderate-to-severe hypoxic-ischemic encephalopathy. (Funded by the Research Council of Norway and the Center for Intervention Science in Maternal and Child Health; NeoSupra ClinicalTrials.gov number, NCT03133572.).

Women's sexual activity and experiences following female genital fistula surgery.

BACKGROUND: Surgical repair has a transformative impact on the lives of women affected by female genital fistula; however, various physical, social, and economic challenges may persist postrepair and prevent complete reengagement in relationships and communities. Nuanced investigation of these experiences is needed to inform programming that aligns with women's reintegration needs. AIM: We investigated the sexual activity resumption, experiences, and concerns of women in Uganda during the year following genital fistula repair surgery. METHODS: Women were recruited from Mulago Hospital between December 2014 and June 2015. We collected data at baseline and 4 times postsurgery about sociodemographic characteristics and physical/psychosocial status; we also assessed sexual interest and satisfaction twice. We performed in-depth interviews with a subset of participants. We analyzed quantitative findings via univariate analyses, and qualitative findings were coded and analyzed thematically. OUTCOMES: We assessed sexual readiness, fears, and challenges following surgical repair of female genital fistula using quantitative and qualitative measures of sexual activity, pain with sex, sexual interest/disinterest, and sexual satisfaction/dissatisfaction. RESULTS: Among the 60 participants, 18% were sexually active at baseline, which decreased to 7% postsurgery and increased to 55% at 1 year after repair. Dyspareunia was reported by 27% at baseline and 10% at 1 year; few described leakage during sex or vaginal dryness. Qualitative findings showed wide variance of sexual experiences. Some reported sexual readiness quickly after surgery, and some were not ready after 1 year. For all, fears included fistula recurrence and unwanted pregnancy. CONCLUSION: These findings suggest that postrepair sexual experiences vary widely and intersect meaningfully with marital and social roles following fistula and repair. In addition to physical repair, ongoing psychosocial support is needed for comprehensive reintegration and the restoration of desired sexuality.

Efficacy of midwife-led role orientation of birth companions on maternal satisfaction and birth outcomes: a randomized control trial in Uganda.

BACKGROUND: The World Health Organization recommends birth companionship for all women in labor. There is insufficient evidence on birth companionship in low-income settings and it is not clear if role orientation impacts effectiveness. The aim of this study was to assess the efficacy of midwife-led role orientation of birth companions of on maternal satisfaction and birth outcomes in a sub-region in Uganda. METHODS: A stepped wedge cluster randomized trial conducted (control n = 240), intervention n = 235) from 4 clusters. Women who had a birth companion, in spontaneously established labor and, expecting a vaginal delivery were eligible. The intervention was "midwife-provided orientation of birth companions". The admitting midwife provided an orientation session for the birth companion on supportive labor techniques. The primary outcome was the chance of having a spontaneous vaginal delivery. Assessors were not blinded. Independent t-test and Chi-Square tests were used to assess the differences by study period. RESULTS: Mean maternal satisfaction rate was significantly higher in the intervention period compared to the control period (P > 0.001). High maternal satisfaction levels were noted among the women who were; at the regional referral hospital, younger, first-time mothers, and unmarried (P < 0.001). Satisfaction with pain management was rated lowest across study periods. Satisfaction with humaneness was rated highest with a higher score in the intervention period (93%) than the control (79.5%). There were no statistically significant differences in the mode of delivery, need to augment labor, length of labor and Apgar scores. CONCLUSION: Midwife-led role orientation of birth companions increased maternal satisfaction. Nevertheless, no significant effect was noted in the mode of delivery, length of labor, Apgar score, and need to augment labor. Findings could inform the integration of birth companions in the admission process of the woman in labor in similar settings. TRIAL REGISTRATION NUMBER: NCT04771325.

Prevalence and effects of menstrual disorders on quality of life of female undergraduate students in Makerere University College of health sciences, a cross sectional survey.

BACKGROUND: Menstrual problems affect as high as 90% of adolescent females and are the main reason for gynecology visits. Dysmenorrhea was the most frequent menstrual disorder for which adolescents and their parents were referred to a physician. Many undergraduate students are adolescents who undergo several hormonal changes that affect menstrual patterns. This study aimed to determine the prevalence of menstrual disorders and to determine the effect of menstrual disorders on quality of life (QOL) of female undergraduate students at Makerere University college of health sciences. METHODS: A cross sectional study design using a self-administered questionnaire. WHO (World Health Organization) QOL-BREF (QOL-Best Available Reference document) questionnaire was used to assess QOL of participants. Collected data was double entered into EPIDATA, and transferred to STATA for analysis. Data was presented using tables, and analyzed using percentages, frequencies, medians, interquartile range, means and standard deviations, t-test and ANOVA were used to establish statistical significance. P < 0.05 was considered statistically significant. RESULTS: Of the participants, 275 were included in the data analysis. The median age of the participants was 21 years with range of 18-39 years and interquartile range of 20-24 years. All the participants had attained menarche. Of the participants, 97.8% (95%CI: 95.2-99.0) (269/275) reported some form of menstrual disorder. Premenstrual symptoms were the commonest disorder (93.8% (95%CI: 90.2-96.1), N = 258) followed by dysmenorrhea (63.6% (95% CI: 57.7-69.1), N = 175), irregular menstruation (20.7% (95%CI: 16.3-25.9), N = 57), frequent menstruation (7.3% 95% CI:4.7-11.0, N = 20) and infrequent menstruation (3.3% (95% CI:1.7-6.2), N = 9). Dysmenorrhea and premenstrual symptoms significantly reduced the QOL scores of participants. CONCLUSION: Menstrual disorders were highly prevalent with negative effects on QOL and class attendance. Efforts should be made to screen and possibly treat menstrual disorders among university students as well as to conduct further studies to elucidate more on the effects of menstrual disorders on quality of life.

Contraceptive preferences and adoption following female genital fistula surgery in Uganda: a mixed-methods study.

BACKGROUND: Female genital fistula, largely caused by prolonged obstructed labour, is treated by surgical repair. Preventing pregnancy for a minimum period post-repair is recommended to ensure adequate healing and optimize post-repair outcomes. METHODS: We examined contraceptive preferences and use among Ugandan fistula patients (n = 60) in the year following genital fistula surgery using mixed-methods. Sexual activity, contraceptive use and pregnancy status were recorded quarterly for 12 months after surgery. In-depth interviews among purposively selected participants (n = 30) explored intimate relationships, sexual experiences, reproductive intentions, and contraceptive use. RESULTS: Median participant age was 28 years and almost half (48%) were married or living with partners. Counselling was provided to 97% of participants on delaying sexual intercourse, but only 59% received counselling on contraception. Sexual activity was reported by 32% after 6 months and 50% after 12 months. Eighty-three percent reported not trying for pregnancy. Among sexually active participants, contraceptive use was low at baseline (36%) but increased to 73% at 12 months. Six (10%) women became pregnant including two within 3 months post-repair. Interview participants who desired children immediately were young, had fewer children, experienced stillbirth at fistula development, and felt pressure from partners. Women adopted contraception to fully recover from fistula surgery and avoid adverse outcomes. Others simply preferred to delay childbearing. Reasons cited for not adopting contraception included misconceptions related to their fertility and to contraceptive methods and insufficient or unclear healthcare provider advice on their preferred methods. CONCLUSIONS: A high proportion of patients were not counselled by healthcare providers on contraception. Provision of comprehensive patient-centred contraceptive counselling at the time of fistula surgery and beyond is important for patients to optimize healing from fistula and minimize recurrence, as well as to meet their own reproductive preferences.

Social support among women with genital fistula in Uganda.

Resulting from prolonged obstructed labour, iatrogenic and traumatic aetiologies, female genital fistula in low-resource settings causes a significant physical and psychosocial burden. Social support is an important mechanism to build resilience to health challenges. This study aimed to understand the role of emotional, informational and tangible social support for Ugandan women affected by fistula. Thirty-three participants who had had fistula surgery 6-24 months prior to the study were recruited from Mulago Hospital in Kampala, Uganda. Data from in-depth interviews (n = 16) and 4 focus group discussions were analysed thematically using a social support framework. Various individuals were key providers of social support across the different domains. They included family, friends, community organisations, and other women affected by fistula. Social support was critical in helping women cope with fistula, access fistula care, and post-repair recovery. Women relied heavily on tangible and emotional support to meet their physical and psychological needs. Support-enhancing interventions for women and their families, particularly those offering emotional and tangible support, may be a promising strategy for improving the experiences and quality of life of women affected by fistula.

Removal of a well-palpable one-rod subdermal contraceptive implant using a dedicated hand-held device or standard technique: a randomized, open-label, non-inferiority trial.

STUDY QUESTION: Is a mechanical hand-held device for removing a single-rod subdermal contraceptive implant safe for implant users? SUMMARY ANSWER: In terms of safety, the device is non-inferior to the standard technique for implant removal. WHAT IS KNOWN ALREADY: An easy-to-use device for removing a subdermal contraceptive implant may be helpful in settings where skilled providers are in short supply. Prior to this study, the only report on the world's first hand-held, mechanical device with build-in incisor was a Swedish study using earlier versions of the product. STUDY DESIGN, SIZE, DURATION: From December 2019 to November 2020, we conducted a three-arm, open-label non-inferiority randomized trial involving 225 Ugandan women to assess safety (primary outcome) and measure implant removal efficacy (secondary outcomes) of a newly developed, hand-held device, compared to the standard removal technique. PARTICIPANTS/MATERIALS, SETTING, METHODS: We randomized participants desiring removal of their one-rod contraceptive implant in a 1:1:1 ratio: standard technique/lidocaine injection, new device/lidocaine patch or new device/lidocaine injection. For primary safety endpoints, we examined removal complications and grouped them according to severity. For secondary endpoints on efficacy, we defined three device outcomes: intact implant removed without additional tools (primary), implant removed allowing implant breakage, but without tools (secondary) and implant removed allowing implant breakage and non-scalpel tools (tertiary). We assessed provider feedback on the device and used chi-square tests for all comparisons. MAIN RESULTS AND THE ROLE OF CHANCE: We recruited 225 participants and randomly assigned (n = 75) to each group. For safety, no primary complications occurred in any treatment group, while only one secondary complication occurred in each treatment group (1%). Primary efficacy was 100% (standard technique), 85% (new device/lidocaine patch) and 73% (new device/lidocaine injection) (P < 0.0001). Secondary efficacy was 100% (standard technique), 92% (new device/lidocaine patch) and 79% (new device/lidocaine injection) (P < 0.0001). Tertiary efficacy was 100% (standard technique), 96% (new device/lidocaine patch) and 91% (new device/lidocaine injection) (P = 0.017). Unsuccessful removals with the new device did not hinder subsequent implant extractions with standard back-up tools. In over 90% of the 150 device procedures, providers agreed or strongly agreed that the product is an acceptable alternative to standard removal technique. LIMITATIONS, REASONS FOR CAUTION: We tested a new removal device in the hands of Ugandan nurses who were adept at standard removal techniques; our estimates of removal efficacy may not apply to lower-level providers who arguably may be the prime beneficiaries of this technology. WIDER IMPLICATIONS OF THE FINDINGS: The study was conducted in a region of the world where the new device could be used to expand access to implant removal services. Intended beneficiaries of the new product are implant users who cannot easily find skilled providers for traditional scalpel-dependent removals and/or users who are intimidated by scalpel procedures, and lower-level providers who can be trained to help deliver services to meet a growing demand. The new device is a safe, acceptable alternative; efficacy was high, but not on par with standard technique. STUDY FUNDING/COMPETING INTEREST(S): Funding for this study was provided by the RemovAid AS of Norway with grants from Research Council of Norway (GLOBVAC number 228319), Bill & Melinda Gates Foundation (grant INV-007571) and SkatteFUNN. M.B. is founder and former CEO of RemovAid AS, Norway. M.B. holds contraceptive rod remover patents (2012 1307156.8 and 2015), pre-removal test (filed) and shares in RemovAid AS. All of the remaining authors' institutions received payments in the form of contracts to help conduct the study; the funds for these contracts emanated from RemovAid AS. TRIAL REGISTRATION NUMBER: NCT04120337. TRIAL REGISTRATION DATE: 9 October 2019. DATE OF FIRST PATIENT'S ENROLMENT: 23 December 2019.

Middle cerebral arterial flow redistribution is an indicator for intrauterine fetal compromise in late pregnancy in low-resource settings: A prospective cohort study.

OBJECTIVE: We aimed to determine the prevalence of abnormal umbilical artery (UA), uterine artery (UtA), middle cerebral artery (MCA) and cerebroplacental ratio (CPR) Doppler, and their relationship with adverse perinatal outcomes in women undergoing routine antenatal care in the third trimester. DESIGN: Prospective cohort. SETTING: Kagadi Hospital, Uganda. POPULATION: Non-anomalous singleton pregnancies. METHODS: Women underwent an early dating ultrasound and a third-trimester Doppler scan between 32 and 40 weeks of gestation, from 2018 to 2020. We handled missing data using multiple imputation and analysed the data using descriptive methods and a binary logistic regression model. MAIN OUTCOME MEASURES: Composite adverse perinatal outcome (CAPO), perinatal death and stillbirth. RESULTS: We included 995 women. The mean gestational age at Doppler scan was 36.9 weeks (SD 1.02 weeks) and 88.9% of the women gave birth in a health facility. About 4.4% and 5.6% of the UA pulsatility index (PI) and UtA PI were above the 95th percentile, whereas 16.4% and 10.4% of the MCA PI and CPR were below the fifth percentile, respectively. Low CPR was strongly associated with stillbirth (OR 4.82, 95% CI 1.09-21.30). CPR and MCA PI below the fifth percentile were independently associated with CAPO; the association with MCA PI was stronger in small-for-gestational-age neonates (OR 3.75, 95% CI 1.18-11.88). CONCLUSION: In late gestation, abnormal UA PI was rare. Fetuses with cerebral blood flow redistribution were at increased risk of stillbirth and perinatal complications. Further studies examining the predictive accuracy and effectiveness of antenatal Doppler ultrasound screening in reducing the risk of perinatal deaths in low- and middle-income countries are warranted. TWEETABLE ABSTRACT: Blood flow redistribution to the fetal brain is strongly associated with stillbirths in low-resource settings.

A qualitative exploratory interview study on birth companion support actions for women during childbirth.

BACKGROUND: The World Health Organization recommends that women are supported continuously throughout labor by a companion of their choice. And, that companions have clearly designated roles and responsibilities to ensure that their presence is beneficial to both the woman and her health care providers. Presently, there is lack of strong evidence regarding specific support actions in relation to women's needs of care. Thus, we aimed to explore birth companion support actions for women during childbirth. METHODS: This was an exploratory descriptive qualitative study conducted between August 2019 and December 2019; at a referral hospital in the Eastern part of Uganda. Ten women were purposively selected: those who were admitted in early labor, expecting a normal delivery, and had fulltime birth companion. Nonparticipant direct observation and in-depth interviews were used to collect data. Latent content analysis was used. RESULTS: Three themes were identified: "Support actions aiding a good childbirth experience", "Support actions hindering coping with labor", and "Women's needs and expectations of care". Support actions aiding a good experience described were; emotional presence, motivation, providing nourishments, messenger activities, body massage for pain relief, assisting in ambulation and coaching. Companion fearful behaviors and disrespectful care in form of unacknowledged needs and hostility from birth companions were reported to hinder coping. The women desired thoughtful communication, trust, for birth companions to anticipate their needs and recognize non perceptive phases of labor to allow them focus on themselves. CONCLUSION: Birth companions from this study largely supported women emotionally, and attended to their physical needs. The greater part of support actions provided were esteemed by the women. Presence of birth companion will be of benefit when individual needs of women are put into consideration. Also, more guidance for birth companions is necessary to boost their role and mitigate shortcomings of their presence during childbirth.

The effect of blister packaging Iron and Folate on adherence to medication and hemoglobin levels among pregnant women at National Referral Hospital antenatal clinics in a low to middle income country: a Randomised Controlled Trial (The IFAd Trial).

INTRODUCTION: Anemia in pregnancy is an important global public health problem. It is estimated that 38% of pregnant women worldwide are anemic. In Africa, literature from observational studies show 20% of maternal deaths are attributed to anemia. In Uganda, 50% of pregnant women have iron deficiency anaemia. The proportion of pregnant women receiving Iron-Folic acid (IFA) supplementation has improved. However, the number of IFA pills consumed is still low. We carried out a randomized controlled trial to determine the effect of dispensing blister and loose packaged IFA pills on adherence measured by count on next return visit and hemoglobin levels among pregnant women at two National Referral Hospitals in Kampala, Uganda. METHODS: This trial was conducted between April and October 2016. Nine hundred fifty pregnant women at ≤28 weeks were randomized to either the blister (intervention arm) or loose (control arm) packaged IFA. The participants completed the baseline measurements and received 30 pills of IFA at enrolment to swallow one pill per day. We assessed adherence by pill count and measured hemoglobin at four and 8 weeks. The results were presented using both intention-to-treat and per-protocol analysis. RESULTS: There were 474 participants in the control and 478 in the intervention arms. Adherence to IFA intake was similar in the two groups at 4th week (40.6 and 39.0%, p = 0.624) and 8th week (51.9 and 46.8%, p = 0.119). The mean hemoglobin level at 4 weeks was higher in the blister than in the loose packaging arms (11.9 + 1.1 g/dl and 11.8 + 1.3 g/dl, respectively; p = 0.02), however, similar at week 8 (12.1 + 1.2 and 12.0 + 1.3, respectively; p = 0.23). However, over the 8-week period blister packaging arm had a higher change in hemoglobin level compared to loose package (blister package 0.6 ± 1.0; loose packaging 0.2 ± 1.1; difference: 0.4 g/dL (95% CI: 0.24-0.51 g/dL); p = 0.001. There were no serious adverse events. CONCLUSIONS: Our results showed no effect of blister packaging on IFA adherence among pregnant women. However, our findings showed that blister packaged group had a higher hemoglobin increase compared to loose iron group. TRIAL REGISTRATION: No. PACTR201707002436264 (20 /07/ 2017).

The role of informational support from women's social networks on antenatal care initiation: qualitative evidence from pregnant women in Uganda.

BACKGROUND: Early and appropriate use of antenatal care services is critical for reducing maternal and neonatal mortality and morbidity. Yet most women in sub-Saharan Africa, including Uganda, do not seek antenatal care until later during pregnancy. This qualitative study explored pregnant women's reliance on social ties for information about initiation of antenatal care. METHODS: We conducted semi-structured, in-depth interviews with 30 pregnant women seeking their first antenatal care visit at Kawempe Referral Hospital in Kampala, Uganda. Recruitment was done purposively to obtain variation by parity and whether women currently had a male partner. Study recruitment occurred from August 25th 2020 - October 26th, 2020. We used thematic analysis following a two-stage coding process, with both deductive and inductive codes. Deductive codes followed the key domains of social network and social support theory. RESULTS: We found that the most important source of information about antenatal care initiation was these women's mothers. Other sources included their mothers-in-law, female elders including grandmothers, and male partners. Sisters and female friends were less influential information sources about antenatal initiation. One of the primary reasons for relying on their own mothers, mothers-in-law, and elder women was due to these women's lived experience with pregnancy and childbirth. Trust in the relationship was also an important factor. Some pregnant women were less likely to rely on their sisters or female friends, either due to lack of trust or these women's lack of experience with pregnancy and childbirth. The advice that pregnant women received from their mothers and others on the ideal timing for antenatal care initiation varied significantly, including examples of misinformation about when to initiate antenatal care. Pregnant women seemed less likely to delay care when more than one social tie encouraged early antenatal care. CONCLUSIONS: Educating women's social networks, especially their mothers, mothers-in-law, and community elders, about the importance of early antenatal care initiation is a promising avenue for encouraging pregnant women to seek care earlier in pregnancy.

Evaluating women's acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians: a mixed methods study.

BACKGROUND: Studies evaluating task sharing in postabortion care have mainly focused on women in first trimester and many lack a qualitative component. We aimed to evaluate patient acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians and also gained a deeper understanding of the patients' lived treatment experiences in Uganda. METHODS: Our mixed methods study combined 1140 structured interview data from a randomized controlled equivalence trial and in-depth interviews (n = 28) among women managed with misoprostol for second trimester incomplete abortion at 14 public health facilities in Uganda. Acceptability, our main outcome, was measured at the 14-day follow-up visit using a structured questionnaire as a composite variable of: 1) treatment experience (as expected/ better than expected/ worse than expected), and 2) satisfaction - if patient would recommend the treatment to a friend or choose the method again. We used generalized mixed effects models to obtain the risk difference in acceptable post abortion care between midwife and physician groups. We used inductive content analysis for qualitative data. RESULTS: From 14th August 2018 to 16th November 2021, we assessed 7190 women for eligibility and randomized 1191 (593 to midwife and 598 to physician). We successfully followed up 1140 women and 1071 (94%) found the treatment acceptable. The adjusted risk difference was 1.2% (95% CI, - 1.2 to 3.6%) between the two groups, and within our predefined equivalence range of - 5 to + 5%. Treatment success and feeling calm and safe after treatment enhanced acceptability while experience of side effects and worrying bleeding patterns reduced satisfaction. CONCLUSIONS: Misoprostol treatment of uncomplicated second trimester incomplete abortion was equally and highly acceptable to women when care was provided by midwives compared with physicians. In settings that lack adequate staffing levels of physicians or where midwives are available to provide misoprostol, task sharing second trimester medical PAC with midwives increases patient's access to postabortion care services. TRIAL REGISTRATION: ClinicalTrials.gov NCT03622073.

Approximately 9.6% of abortion-related deaths occur in Sub-Saharan Africa. These deaths can be prevented if unintended pregnancies are avoided, women can access safe abortions within the expectations of the country's laws, and post abortion care (PAC) services are provided equitably. Previous research shows that women with abortion complications in the first trimester of pregnancy can be treated with misoprostol by either midwives or physicians. This sharing of tasks between the midwives and physicians is safe, effective, and acceptable. However, there is a gap in evidence on task sharing in the second trimester. To check practicability of task sharing in second trimester, we aimed to evaluate patient acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians and also gained a deeper understanding of the patients' lived treatment experiences. Our study therefore combined quantitative and qualitative approaches. Women's acceptability of misoprostol treatment for incomplete second trimester abortion was found to be equally acceptable when provided by midwives compared with physicians. Treatment success, feeling calm and safe after treatment increased acceptability, while experience of side effects and worrying bleeding patterns reduced satisfaction. Counselling of women may address some of these problems since it provides reassurance and reduces anxiety. In settings that lack adequate staffing levels of physicians or where midwives are available to provide misoprostol, task sharing second trimester medical PAC with midwives increases patient's access to PAC services.

Feasibility and acceptability of mobile phone data collection for longitudinal follow-up among patients treated for obstetric fistula in Uganda.

Rapid dissemination of mobile technology provides substantial opportunity for overcoming challenges reaching rural and marginalized populations. We assessed feasibility and acceptability of longitudinal mobile data capture among women undergoing fistula surgery in Uganda (n = 60) in 2014-2015. Participants were followed for 12 months following surgery, with data captured quarterly, followed by interviews at 12 months. Participant retention was high (97%). Most respondents reported no difficulty with mobile data capture (range 93%-100%), and preferred mobile interview (88%-100%). Mobile data capture saved 1000 person-hours of transit and organizational time. Phone-based mobile data collection provided social support. Our results support this method for longitudinal studies among geographically and socially marginalized populations.

Infant Exposure to Dolutegravir Through Placental and Breast Milk Transfer: A Population Pharmacokinetic Analysis of DolPHIN-1.

BACKGROUND: Rapid reduction in human immunodeficiency virus (HIV) load is paramount to prevent peripartum transmission in women diagnosed late in pregnancy. We investigated dolutegravir population pharmacokinetics in maternal plasma, umbilical cord, breast milk, and infant plasma samples from DolPHIN-1 participants (NCT02245022) presenting with untreated HIV late in pregnancy (28-36 weeks gestation). METHODS: Pregnant women from Uganda and South Africa were randomized (1:1) to daily dolutegravir (50 mg/d) or efavirenz-based therapy. Dolutegravir pharmacokinetic sampling (0-24 hours) was undertaken 14 days after treatment initiation and within 1-3 weeks after delivery, with matched maternal and cord samples at delivery. Mothers were switched to efavirenz, and maternal and infant plasma and breast milk samples were obtained 24, 48, or 72 hours after the switch. Nonlinear mixed-effects modeling was used to describe dolutegravir in all matrices and to evaluate covariates. RESULTS: A total of 28 women and 22 infants were included. Maternal dolutegravir was described by a 2-compartment model linked to a fetal and breast milk compartment. Cord and breast milk to maternal plasma ratios were 1.279 (1.209-1.281) and 0.033 (0.021-0.050), respectively. Infant dolutegravir was described by breast milk-to-infant and infant elimination rate constants. No covariate effects were observed. The median predicted infant dolutegravir half-life and median time to protein-adjusted 90% inhibitory concentration (0.064 mg/L) for those above this threshold were 37.9 (range, 22.1-63.5) hours and 108.9 (18.6-129.6) hours (4.5 [0.8-5.4] days) (n = 13), respectively. CONCLUSIONS: Breastfeeding contributed relatively little to infant plasma exposure, but a median of 4.5 days of additional prophylaxis to some of the breastfed infants was observed after cessation of maternal dolutegravir (3-15 days postpartum), which waned with time postpartum as transplacental dolutegravir cleared.

Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth.

BACKGROUND: Postpartum hemorrhage is the most common cause of maternal death. Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but it requires cold storage, which is not available in many countries. In a large trial, we compared a novel formulation of heat-stable carbetocin with oxytocin. METHODS: We enrolled women across 23 sites in 10 countries in a randomized, double-blind, noninferiority trial comparing intramuscular injections of heat-stable carbetocin (at a dose of 100 µg) with oxytocin (at a dose of 10 IU) administered immediately after vaginal birth. Both drugs were kept in cold storage (2 to 8°C) to maintain double-blinding. There were two primary outcomes: the proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and the proportion of women with blood loss of at least 1000 ml. The noninferiority margins for the relative risks of these outcomes were 1.16 and 1.23, respectively. RESULTS: A total of 29,645 women underwent randomization. The frequency of blood loss of at least 500 ml or the use of additional uterotonic agents was 14.5% in the carbetocin group and 14.4% in the oxytocin group (relative risk, 1.01; 95% confidence interval [CI], 0.95 to 1.06), a finding that was consistent with noninferiority. The frequency of blood loss of at least 1000 ml was 1.51% in the carbetocin group and 1.45% in the oxytocin group (relative risk, 1.04; 95% CI, 0.87 to 1.25), with the confidence interval crossing the margin of noninferiority. The use of additional uterotonic agents, interventions to stop bleeding, and adverse effects did not differ significantly between the two groups. CONCLUSIONS: Heat-stable carbetocin was noninferior to oxytocin for the prevention of blood loss of at least 500 ml or the use of additional uterotonic agents. Noninferiority was not shown for the outcome of blood loss of at least 1000 ml; low event rates for this outcome reduced the power of the trial. (Funded by Merck Sharpe & Dohme; CHAMPION Australian New Zealand Clinical Trials Registry number, ACTRN12614000870651 ; EudraCT number, 2014-004445-26 ; and Clinical Trials Registry-India number, CTRI/2016/05/006969 .).

Antenatal Doppler ultrasound implementation in a rural sub-Saharan African setting: exploring the perspectives of women and healthcare providers.

BACKGROUND: The World Health Organization recommends research to evaluate the effects of a single third trimester Doppler ultrasound examination on preventable deaths in unselected-risk pregnancies, particularly in low- and middle-income countries (LMICs) where the evidence base is scarce. While evaluating such technologies, researchers often ignore women and health care provider perspectives. This study explored the views and experiences of women and healthcare providers regarding the use of advanced ultrasound technology to optimize the health of mothers and their babies in a rural community in mid-western Uganda. METHODS: We enrolled 53 mothers and 10 healthcare providers, and captured data on their perceptions, barriers, and facilitators to the use of Doppler ultrasound technology using focus group discussions, semi-structured interviews and observations. Using qualitative content analysis, we inductively coded the transcripts in ATLAS.ti 8.0, detecting emerging themes. RESULTS: Women were afraid that ultrasound would harm them or their fetuses and many of them had never seen an ultrasound scan. The majority of the women found their partners supportive to attend antenatal care and use ultrasound services. Healthcare providers in Kagadi Hospital were unfamiliar with Doppler technology and using it to guide clinical decisions. Other barriers to the implementation of Doppler ultrasound included shortage of trained local staff, insufficient equipment, long distance to and from the hospital, and frequent power cuts. CONCLUSIONS: We found limited exposure to Doppler ultrasound technology among women and healthcare providers in mid-western Uganda. Engaging male partners may potentially influence the likelihood of accepting and using it to improve the health of women and their fetuses while wide spread myths and misconceptions about it may be changed by community engagement. Healthcare workers experienced difficulties in offering follow-up care to mothers detected with complications and Doppler ultrasound required a high level of training. While introducing advanced ultrasound machines to weak health systems, it is important to adequately train healthcare providers to avoid inappropriate interventions based on misinterpretation of the findings, consider where it is likely to be most beneficial, and embed it with realistic clinical practice guidelines.

Globally, nearly three million babies are stillborn every year, but most especially in low- and middle-income countries like Uganda. One of the factors contributing to a high number of stillbirths in low-income countries is the difficulty in identifying complications and accessing high quality care during pregnancy. Although antenatal Doppler scans are being widely used to diagnose complications in high-risk pregnancies in developed countries, studies evaluating it in LMICs are needed before it is implemented on a wide scale. We engaged 53 mothers, eight health workers from a hospital and two healthcare managers from a local government in Uganda to attain their opinions about Doppler ultrasound. We found that spousal involvement may promote acceptance and use of ultrasound services. However, the health workers did not have adequate knowledge about Doppler technology and using it for the benefit of mothers and the mothers feared that ultrasound procedures might harm them or their unborn babies. Making matters worse, the hospital faced frequent power cuts that affected the use of the equipment. Further, mothers must cover a long distance to access the hospital and its services. To reduce the number of babies dying during pregnancy or a few days after birth in Uganda and similar low-resource settings using Doppler technology, it is essential to strengthen the health systems. Starting with the training of healthcare providers to equipping and stabilizing power supply in health facilities, and educating the public about critical health procedures to break myths and misconceptions.

Cost of hospital care of women with postpartum haemorrhage in India, Kenya, Nigeria and Uganda: a financial case for improved prevention.

OBJECTIVE: Access to quality, effective lifesaving uterotonics in low and middle-income countries (LMICs) remains a major barrier to reducing maternal deaths from postpartum haemorrhage (PPH). Our objective was to assess the costs of care for women who receive different preventative uterotonics, and with PPH and no-PPH so that the differences, if significant, can inform better resource allocation for maternal health care. METHODS: The costs of direct hospital care of women who received oxytocin or heat-stable carbetocin for prevention of PPH in selected tertiary care facilities in India, Kenya, Nigeria, and Uganda were assessed. We collected data from all women who had PPH, as well as a random sample of women without PPH. Cost data was collected for the cost of stay, PPH interventions, transfusions and medications for 2966 women. We analyzed the difference in cost of care at a facility level between women who experienced a PPH event and those who did not. Key findings The mean cost of care of a woman experiencing PPH in the study sites in India, Kenya, Nigeria, and Uganda exceeded the cost of care of a woman who did not experience PPH by between 21% and 309%. There was a large variation in cost across hospitals within a country and across countries. CONCLUSION: Our results quantify the increased cost of PPH of up to 4.1 times that for a birth without PPH. PPH cost information can help countries to evaluate options across different conditions and in the formulation of appropriate guidelines for intrapartum care, including rational selection of quality-assured, effective medicines. This information can be applied to national assessment and adaptation of international recommendations such as the World Health Organization's recommendations on uterotonics for the prevention of PPH or other interventions used to treat PPH. Trial registration HRP Trial A65870; UTN U1111-1162-8519; ACTRN12614000870651; CTRI/2016/05/006969, EUDRACT 2014-004445-26. Date of registration 14 August 2014 Access to quality, effective lifesaving medicines in low and middle-income countries remains a major barrier to reducing maternal deaths from bleeding after childbirth. Information on to what extent treatments for bleeding increases the cost of care of women after childbirth is important for informed resource allocation. We collected data from all women who had bleeding after childbirth, as well as a random sample of women without bleeding in selected hospitals in India, Kenya, Nigeria, and Uganda. Cost data was collected for the cost of stay and interventions to manage bleeding for 2966 women. We compared the difference in cost of care between women who experienced a bleeding event and those who did not. The mean cost of care of a woman with bleeding in the study sites exceeded the cost of care of a woman who did not experience PPH by between 21% and 309%. There was a large variation in cost across hospitals within a country and across countries. Our results indicate an increased cost of bleeding of up to 4.1 times that for birth without bleeding. Effective prevention reduces the cost of care. Cost information can help countries to evaluate options across different conditions and in the formulation of appropriate guidelines for intrapartum care, including rational selection of quality-assured, effective medicines. This information can be applied to national assessment and adaptation of international recommendations such as the World Health Organization's recommendations on medications for the prevention of bleeding after childbirth or other interventions used to treat bleeding.

Comparative analysis of perinatal outcomes and birth defects amongst adolescent and older Ugandan mothers: evidence from a hospital-based surveillance database.

BACKGROUND: Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12-19 years) and mothers (age 20-34 years) in four urban hospitals. METHODS: Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson's chi-square. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to mothers 20-34 years. RESULTS: A total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. Adolescent mothers had an increased risk of preterm delivery (aOR: 1.14; CI 1.06-1.23), low birth weight (aOR: 1.46; CI 1.34-1.59), and early neonatal deaths (aOR: 1.58; CI 1.23-2.02). Newborns of adolescent mothers had an increased risk of major external birth defects (aOR: 1.33; CI 1.02-1.76), specifically, gastroschisis (aOR: 3.20; CI 1.12-9.13) compared to mothers 20-34 years. The difference between the prevalence of gastroschisis among adolescent mothers (7.3 per 10,000 births; 95% CI 3.7-14.3) was statistically significant when compared to mothers 20-34 years (1.6 per 10,000 births; 95% CI 0.9-2.6). CONCLUSIONS: This study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20-34 years, similar to findings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population.

Adolescent pregnancies are a global problem occurring in high-, middle-, and low-income countries with Uganda having one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes, including major external birth defects, between adolescents, (age 12­19 years) and mothers (age 20­34 years) in four urban hospitals.All informative births, including live births, stillbirths, and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2018 were examined. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes.Of the 100,189 births, 11.0% were among adolescent mothers and 89.0% among mothers (20­34 years). Adolescent mothers were more likely than mothers (20­34 years) to have an infant with preterm delivery, low birth weight, early neonatal death, and major external birth defects. Adolescent pregnancies were also associated with an increased risk of gastroschisis when compared to mothers (20­34 years).In conclusion, this study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20­34 years. Research on the potential underlying causes or mechanisms for these adverse outcomes among adolescent births is necessary to identify possible interventions.