No association of a Vascular endothelial growth factor A (VEGFA) gene polymorphism with pre-eclampsia among pregnant women in Uganda.

BACKGROUND: Vascular endothelial growth factor A (VEGFA) is a major angiogenic factor that plays an important role in the formation of blood vessels during embryonic development. VEGFA has been implicated in the pathophysiology of pre-eclampsia (PE), since pre-eclamptic women present with reduced levels of free circulating VEGFA. The 3' untranslated region (3'-UTR) of the VEGFA gene consists of elements that regulate the transcription and hence expression of the VEGFA protein in circulation. Hence it is suggested that variations thereof could underlie the reduced VEGFA levels observed in pre-eclamptic women. The purpose of this study was to investigate presence of the + 936C/T polymorphism, a common single nucleotide polymorphism (SNP) in the 3'-UTR of the VEGFA gene, and determine its association with PE among pregnant women in Uganda. RESULTS: There was no significant difference observed in the allele and genotype frequencies of the + 936C/T 3' UTR-VEGFA polymorphism between pre-eclamptic and normotensive pregnant women (P > 0.05). Additionally, there was no significant difference in the median plasma levels of free VEGFA among women with the wild type, CT and TT genotypes of the + 936C/T VEGFA polymorphism (median = 0.84 pg/mL (IQR = 0.39-1.41) Vs 1.05 (0.61-1.18) Vs 1.05 (1.05-1.05) respectively, p-value = 0.7161). CONCLUSIONS: These study findings indicate that the + 936C/T 3' UTR-VEGFA polymorphism had no significant association with increased susceptibility to PE among women in Uganda. Further studies with a larger sample size are recommended.

Randomized trial to compare acceptability of magnesium sulphate administration for preeclampsia and eclampsia: Springfusor pump versus standard of care.

INTRODUCTION: In low-resource settings, magnesium sulphate (MgSO4) for preeclampsia is administered majorly through an injection into the gluteal muscles 4-hourly for 24 hours. The repeated injections are very painful and may lead to infection, abscess formation, and reduced compliance. OBJECTIVE: To determine the acceptability of Springfusor® pump for the administration of Magnesium Sulphate in preeclampsia and eclampsia. DESIGN: Randomized Open Label Clinical Trial. METHODS: The study was conducted at Kawempe National Referral Hospital. Eligible women had a systolic blood pressure of ≥140mmHg and or diastolic blood pressure >90mmHg, proteinuria ≥+1, and the physician's decision to start on MgSO4. Four-hundred-ninety-six participants were randomized to a Springfusor® pump group (n = 248) or control (standard of care) (n = 248) administration of MgSO4. Intervention group had a loading dose (4gm of 50% MgSO4 intravenously over 20 minutes) and maintenance therapy (1gm of 50% MgSO4 intravenously per hour for 24 hours) administered using the Springfusor®. The standard of care (SOC) group received a loading dose of 4gm of 20% MgSO4 IV over 15-20 minutes, followed by 10gm of 50% MgSO4 intramuscular (5gm in each buttock) and a maintenance dose of 5gm of 50% MgSO4 was administered IM every 4 hours for 24 hours. Both arms received the rest of the care for preeclampsia/eclampsia as per the hospital guidelines. Acceptability of the method of administration was assessed using a Likert scale (1-5; 1 and 2: acceptable and 3-5: unacceptable). Pain at the site of MgSO4 administration was assessed using a Visual Analogue Scale 1-7, (1 minimal pain and 7 worst pain). Comparisons were assessed with the Chi-square test, Mann Whitney-Wilcoxon test, and Students' t-test. RESULTS: Intervention arm; was more acceptable than the standard of care arm, (95.3% vs70.3%; p<0.001), had a lower median pain score, (2(CI: 2-2), vs 4(CI: 4-5) p<0.001), and fewer side effects. Maternal mortality was comparable between groups (0.8% in the intervention arm vs 1.2% in the IM arm). TRIAL REGISTRATION: Trial No PACTR201712002887266 (https://pactr.samrc.ac.za/).

Obstetric referrals, complications and health outcomes in maternity wards of large hospitals during the COVID-19 pandemic: a mixed methods study of six hospitals in Guinea, Nigeria, Uganda and Tanzania.

OBJECTIVES: The COVID-19 pandemic affected provision and use of maternal health services. This study describes changes in obstetric complications, referrals, stillbirths and maternal deaths during the first year of the pandemic and elucidates pathways to these changes. DESIGN: Prospective observational mixed-methods study, combining monthly routine data (March 2019-February 2021) and qualitative data from prospective semi-structured interviews. Data were analysed separately, triangulated during synthesis and presented along three country-specific pandemic periods: first wave, slow period and second wave. SETTING: Six referral maternities in four sub-Saharan African countries: Guinea, Nigeria, Tanzania and Uganda. PARTICIPANTS: 22 skilled health personnel (SHP) working in the maternity wards of various cadres and seniority levels. RESULTS: Percentages of obstetric complications were constant in four of the six hospitals. The percentage of obstetric referrals received was stable in Guinea and increased at various times in other hospitals. SHP reported unpredictability in the number of referrals due to changing referral networks. All six hospitals registered a slight increase in stillbirths during the study period, the highest increase (by 30%-40%) was observed in Uganda. Four hospitals registered increases in facility maternal mortality ratio; the highest increase was in Guinea (by 158%), which had a relatively mild COVID-19 epidemic. These increases were not due to mortality among women with COVID-19. The main pathways leading to these trends were delayed care utilisation and disruptions in accessing care, including sub-optimal referral linkages and health service closures. CONCLUSIONS: Maternal and perinatal survival was negatively affected in referral hospitals in sub-Saharan Africa during COVID-19. Routine data systems in referral hospitals must be fully used as they hold potential in informing adaptations of maternal care services. If combined with information on women's and care providers' needs, this can contribute to ensuring continuation of essential care provision during emergency.

A mixed-methods study of maternal health care utilisation in six referral hospitals in four sub-Saharan African countries before and during the COVID-19 pandemic.

INTRODUCTION: In sub-Saharan Africa, referral hospitals are important sources of key maternal health services, especially during a crisis such as the COVID-19 pandemic. This study prospectively assessed the effect of the COVID-19 pandemic on maternal health service utilisation in six large referral hospitals in Guinea, Nigeria, Tanzania and Uganda during the first year of the pandemic. METHODS: Mixed-methods design combining three data sources: (1) quantitative data based on routine antenatal, childbirth and postnatal care data collected March 2019-February 2021, (2) qualitative data from recurring rounds of semi-structured interviews conducted July 2020-February 2021 with 22 maternity skilled heath personnel exploring their perceptions of service utilisation and (3) timeline data of COVID-19 epidemiology, global, national and hospital-level events. Qualitative and quantitative data were analysed separately, framed based on the timeline analysis and triangulated when reporting. RESULTS: Three periods including a first wave, slow period and second wave were identified. Maternal health service utilisation was lower during the pandemic compared with the prepandemic year in all but one selected referral hospital. During the pandemic, service utilisation was particularly lower during the waves and higher or stable during the slow period. Fear of being infected in hospitals, lack of transportation, and even when available, high cost of transportation and service closures were key reasons affecting utilisation during the waves. However, community perception that the pandemic was over or insinuation by Government of the same appeared to stabilise use of referral hospitals for childbirth. CONCLUSION: Utilisation of maternal health services across the continuum of care varied through the different periods and across countries. In crisis situations such as COVID-19, restrictions and service closures need to be implemented with consideration given to alternative options for women to access and use services. Information on measures put in place for safe hospital use should be communicated to women.

'We are not going to shut down, because we cannot postpone pregnancy': a mixed-methods study of the provision of maternal healthcare in six referral maternity wards in four sub-Saharan African countries during the COVID-19 pandemic.

INTRODUCTION: Referral hospitals in sub-Saharan Africa are located in crowded urban areas, which were often epicentres of the COVID-19 pandemic. This paper prospectively assesses how maternal healthcare was provided in six referral hospitals in Guinea, Nigeria, Tanzania and Uganda during the first year of the COVID-19 pandemic. METHODS: Mixed-methods design using three data sources: (1) qualitative data from repeated rounds of semi-structured interviews conducted between July 2020 and February 2021 with 22 maternity skilled heath personnel (SHP) on perceptions of care provision; (2) quantitative monthly routine data on caesarean section and labour induction from March 2019 to February 2021; and (3) timeline data of COVID-19 epidemiology, national and hospital-level events. Qualitative and quantitative data were analysed separately, framed based on timeline analysis, and triangulated during reporting. RESULTS: We identified three periods: first wave, slow period and second wave. The first wave was challenging for SHP given little knowledge about COVID-19, lack of infection prevention and control training, and difficulties reaching workplace. Challenges that persisted beyond the first wave were shortage of personal protective equipment and no rapid testing for women suspected with COVID-19. We noted no change in the proportion of caesarean sections during the pandemic, and a small increase in the proportion of labour inductions. All hospitals arranged isolation areas for women suspected/confirmed with COVID-19 and three hospitals provided care to women with suspected/confirmed COVID-19. Breastfeeding was not discouraged and newborns were not separated from mothers confirmed with COVID-19. Care provision was maintained through dedication of SHP, support from hospital management and remote communication between SHP. CONCLUSION: Routine maternal care provision was maintained in referral hospitals, despite first wave challenges. Referral hospitals and SHP contributed to guideline development for pregnant women suspected/confirmed with COVID-19. Maternity SHP, women and pregnancy must always be included in priority setting when responding to health system shocks, including outbreaks.

Circulating levels of angiogenic factors and their association with preeclampsia among pregnant women at Mulago National Referral Hospital in Uganda.

Preeclampsia (PE) is a major cause of maternal and new-born morbidity and mortality. Angiogenic factors contribute a major role in the vascular dysfunction associated with PE. We investigated the circulating levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and soluble Feline McDonough Sarcoma (fms)-like tyrosine kinase-1 (sFlt1), their association with PE and diagnostic performance of disease among pregnant women in Uganda. Using a case-control study design, 106 women with PE and 106 with normal pregnancy were enrolled. Demographic and clinical characteristics, and anticoagulated blood samples were collected from participants. Plasma VEGF, PlGF and sFlt1 levels were measured using Luminex and enzyme linked immunosorbent assays (ELISA). Conditional logistic regression was used to explore association of angiogenic factors with PE and receiver operating characteristic analysis was performed to investigate PE diagnostic performance. Levels of VEGF and PIGF were significantly lower in cases compared to controls (VEGF: median = 0.71 pg/ml (IQR = 0.38-1.11) Vs 1.20 pg/ml (0.64-1.91), p-value<0.001 and PlGF: 2.20 pg/ml (1.08-5.86) Vs 84.62 pg/ml (34.00-154.45), p-value<0.001). Plasma levels of sFlt1 were significantly higher in cases than controls (median = 141.13 (71.76-227.10) x103 pg/ml Vs 19.86 (14.20-29.37) x103 pg/ml). Increasing sFlt1 levels were associated with increased likelihood of PE (aOR = 4.73; 95% CI, 1.18-19.01; p-value = 0.0287). The sFlt1/PlGF ratio and sFlt1 had a better performance for diagnosis of PE, with AUC = 0.95 (95% CI, 0.93-0.98) followed by PlGF with AUC = 0.94 (95% CI, 0.91-0.97). Therefore, sFlt1, sFlt1/PlGF ratio and PlGF are potential candidates for incorporation into algorithms for PE diagnosis in the Ugandan population.