The global transition to use of dolutegravir (DTG) in WHO-preferred regimens for HIV treatment is limited by lack of knowledge on use in pregnancy. Here we assessed the relationship between drug concentrations (pharmacokinetics, PK), including in breastmilk, and impact on viral suppression when initiated in the third trimester (T3). In DolPHIN-1, HIV-infected treatment-naïve pregnant women (28–36 weeks of gestation, age 26 (19–42), weight 67kg (45–119), all Black African) in Uganda and South Africa were randomised 1:1 to dolutegravir (DTG) or efavirenz (EFV)-containing ART until 2 weeks post-partum (2wPP), between 9^th March 2017 and 16^th January 2018, with follow-up until six months postpartum. The primary endpoint was pharmacokinetics of DTG in women and breastfed infants; secondary endpoints included maternal and infant safety and viral suppression. Intensive pharmacokinetic sampling of DTG was undertaken at day 14 and 2wPP following administration of a medium-fat breakfast, with additional paired sampling between maternal plasma and cord blood, breastmilk and infant plasma. No differences in median baseline maternal age, gestation (31 vs 30 weeks), weight, obstetric history, viral load (4.5 log₁₀ copies/mL both arms) and CD4 count (343 vs 466 cells/mm³) were observed between DTG (n = 29) and EFV (n = 31) arms. Although DTG C_trough was below the target 324ng/mL (clinical EC90) in 9/28 (32%) mothers in the third trimester, transfer across the placenta (121% of plasma concentrations) and into breastmilk (3% of plasma concentrations), coupled with slower elimination, led to significant infant plasma exposures (3–8% of maternal exposures). Both regimens were well-tolerated with no significant differences in frequency of adverse events (two on DTG-ART, one on EFV-ART, all considered unrelated to drug). No congenital abnormalities were observed. DTG resulted in significantly faster viral suppression (P = 0.02) at the 2wPP visit, with median time to <50 copies/mL of 32 vs 72 days. Limitations related to the requirement to initiate EFV-ART prior to randomisation, and to continue DTG for only two weeks postpartum. Despite low plasma DTG exposures in the third trimester, transfer across the placenta and through breastfeeding was observed in this study, with persistence in infants likely due to slower metabolic clearance. HIV RNA suppression <50 copies/mL was twice as fast with DTG compared to EFV, suggesting DTG has potential to reduce risk of vertical transmission in mothers who are initiated on treatment late in pregnancy. clinicaltrials.gov NCT02245022

Prolonged second stage of labour is a major cause of perinatal and maternal morbidity and mortality in low-income countries. Vacuum extraction is a proven effective intervention, hardly used in Africa. Many authors and organisations recommend (re)introduction of vacuum extraction, but successful implementation has not been reported. In 2012, a program to increase the use of vacuum extraction was implemented in Mulago Hospital, Uganda. The program consisted of development of a vacuum extraction guideline, supply of equipment and training of staff. The objective of this study was to investigate the impact of the program. Audit of a quality improvement intervention with before and after measurement of outcome parameters. Setting: Mulago Hospital, the national referral hospital for Uganda with approximately 33 000 deliveries per year. It is the university teaching hospital for Makerere University and most of the countries doctors and midwives are trained here. Data was collected from hospital registers and medical files for a period of two years. Main outcome measures were vacuum extraction rate, intrapartum stillbirth, neonatal death, uterine rupture, maternal death and decision to delivery interval. Mode of delivery and outcome of 12 143 deliveries before and 34 894 deliveries after implementation of the program were analysed. The vacuum extraction rate increased from 0.6 – 2.4 % of deliveries (p < 0.01) and was still rising after 18 months. There was a decline in intrapartum stillbirths from 34 to 26 per 1000 births (-23.6 %, p < 0.01) and women with uterine rupture from 1.1 – 0.8 per 100 births (-25.5 %, p < 0.01). Decision to delivery interval for vacuum extraction was four hours shorter than for caesarean section. A program to increase the use of vacuum extraction was successful in a high-volume university hospital in sub-Saharan Africa. The use of vacuum extraction increased. An association with improved maternal and perinatal outcome is strongly suggested. We recommend broad implementation of vacuum extraction, whereby university hospitals like Mulago Hospital can play an important role.To support implementation, we recommend further research into outcome of vacuum extraction and into vacuum extraction devices for low-income countries. Such studies are now in progress at Mulago Hospital.

The appropriate use of the Partograph allows early identification of labour related complications and prevents deaths. We, therefore, sought to determine the level of Partograph completion and healthcare worker perspectives towards its utilization. This study had two components; a hospital-based cross-sectional descriptive chart review at the Mulago National Referral Hospital, Kampala, Uganda and a qualitative study involving four Focus Group Discussions (FGDs) with ward nurses, midwives and postgraduate residents. Data from the FGDs were analyzed using thematic -content analysis in Open Code software. The quantitative data were summarized using descriptive statistical analysis, means and proportions. Among the 355 Partographs reviewed, 79.1% had incomplete documentation of age, 52.7% gravidity, and 3.2% parity. In about 61%, the specific parameters for fetal monitoring, maternal monitoring and labour progress were incomplete. From the FGDs, the healthcare workers reported being unable to complete the Partographs due to the overwhelming numbers of expectant mothers and other staff responsibilities. Congestion in the maternity ward reduced the Partograph completion rates. The availability of other monitoring tools, limitation in skills, inadequate equipment and supplies, and the state of the mother at the presentation to the hospital all made Partograph use and completion challenging. The majority of Partographs started by health workers were incomplete. The time required to document, health system challenges, status of mother at presentation, and the high workload undermined completion of the Partograph at this high volume facility.

Objectives To critically explore and describe the pathways that women who require emergency obstetrics and newborn care (EmONC) go through and to understand the delays in accessing EmONC after reaching a health facility in a conflict-affected setting. Design This was a qualitative study with two units of analysis: (1) critical incident technique (CIT) and (2) key informant interviews with health workers, patients and attendants. Setting Thirteen primary healthcare centres, one general private-not-for-profit hospital, one regional referral hospital and one teaching hospital in northern Uganda. Participants Forty-nine purposively selected health workers, patients and attendants participated in key informant interviews. CIT mapped the pathways for maternal deaths and near-misses selected based on critical case purposive sampling. Results After reaching the health facility, a pregnant woman goes through a complex pathway that leads to delays in receiving EmONC. Five reasons were identified for these delays: shortage of medicines and supplies, lack of blood and functionality of operating theatres, gaps in staff coverage, gaps in staff skills, and delays in the interfacility referral system. Shortage of medicines and supplies was central in most of the pathways, characterised by three patterns: delay to treat, back-and-forth movements to buy medicines or supplies, and multiple referrals across facilities. Some women also bypassed facilities they deemed to be non-functional. Conclusion Our findings show that the pathway to EmONC is precarious and takes too long even after making early contact with the health facility. Improvement of skills, better management of the meagre human resource and availing essential medical supplies in health facilities may help to reduce the gaps in a facility’s emergency readiness and thus improve maternal and neonatal outcomes.

Background: Every day approximately 810 women die from complications related to pregnancy and childbirth worldwide. Around two thirds of these deaths happen in sub-Saharan Africa. One of the strategies to decrease these numbers is improving the quality of care by emergency obstetric simulation-based training. The effectiveness of such training programs depends on the program’s instructional design. Objective: This review gives an overview of studies about emergency obstetric simulation-based training and examines the applied instructional design of the training programs in sub-Saharan and Central Africa. Methods: We searched Medline, Embase and Cochrane Library from inception to May 2021. Peer-reviewed articles on emergency obstetric, postgraduate, simulation-based training in sub-Saharan and Central Africa were included. Outcome measures were categorized based on Kirkpatrick’s levels of training evaluation. The instructional design was evaluated by using the ID-SIM questionnaire. Findings: In total, 47 studies met the inclusion criteria. Evaluation on Kirkpatrick level 1 showed positive reactions in 18 studies. Challenges and recommendations were considered. Results on knowledge, skills, and predictors for these results (Kirkpatrick level 2) were described in 29 studies. Retention as well as decay of knowledge and skills over time were presented. Results at Kirkpatrick level 3 were measured in 12 studies of which seven studies demonstrated improvements of skills on-the-job. Improvements of maternal and neonatal outcomes were described in fifteen studies and three studies reported on cost-estimations for training rollout (Kirkpatrick level 4). Instructional design items were heterogeneously applied and described. Conclusions: Results of 47 studies indicate evidence that simulation-based training in sub-Saharan and Central Africa can have a positive impact across all four levels of Kirkpatrick’s training evaluation model. However, results were not consistent across all studies and the effects vary over time. A detailed description of instructional design features in future publications on simulation-based training will contribute to a deeper understanding of the underlying mechanisms that determine why certain training programs are more effective in improving maternal and neonatal healthcare outcomes than other.

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 25^th 2020 – October 26^th, 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.