The MamaMiso study of self-administered misoprostol to prevent bleeding after childbirth in rural Uganda: a community-based, placebo-controlled randomised trial

BACKGROUND: 600 mcg of oral misoprostol reduces the incidence of postpartum haemorrhage (PPH), but in previous research this medication has been administered by health workers. It is unclear whether it is also safe and effective when self-administered by women. METHODS: This placebo-controlled, double-blind randomised trial enrolled consenting women of at least 34 weeks gestation, recruited over a 2-month period in Mbale District, Eastern Uganda. Participants had their haemoglobin measured antenatally and were given either 600 mcg misoprostol or placebo to take home and use immediately after birth in the event of delivery at home. The primary clinical outcome was the incidence of fall in haemoglobin of over 20% in home births followed-up within 5 days. RESULTS: 748 women were randomised to either misoprostol (374) or placebo (374). Of those enrolled, 57% delivered at a health facility and 43% delivered at home. 82% of all medicine packs were retrieved at postnatal follow-up and 97% of women delivering at home reported self-administration of the medicine. Two women in the misoprostol group took the study medication antenatally without adverse effects. There was no significant difference between the study groups in the drop of maternal haemoglobin by >20% (misoprostol 9.4% vs placebo 7.5%, risk ratio 1.11, 95% confidence interval 0.717 to 1.719). There was significantly more fever and shivering in the misoprostol group, but women found the medication highly acceptable. CONCLUSIONS: This study has shown that antenatally distributed, self-administered misoprostol can be appropriately taken by study participants. The rarity of the primary outcome means that a very large sample size would be required to demonstrate clinical effectiveness. TRIAL REGISTRATION: This study was registered with the ISRCTN Register (ISRCTN70408620)

Prospective cohort study comparing outcomes between vacuum extraction and second-stage cesarean delivery at a Ugandan tertiary referral hospital

Research into fetal development and medicin

A classification of grammar-infused templates for ontology and model verbalisation

Involving domain-experts in the development, maintenance, and use of knowledge organisation systems can be made easier through the introduction of easy-to-use interfaces that are based on natural language. Well resourced languages make use of natural language generation techniques to provide such interfaces. In particular, they often make use of templates combined with computational grammar rules to generate grammatically complex text. However, there is no model of pairing templates and computational grammar rules to ensure suitability for less-resourced languages. These languages require a modular design that ensures grammar detachability so as to allow grammar re-use across domains and applications. In this paper, we present a model and classification scheme for grammar-infused templates suited for less-resourced languages and classify existing systems that make use of them. We have found that of the 15 systems that pair templates and grammar rules, and their 11 distinct template types, 13 have support for detachable grammars

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

Prognostic accuracy of antenatal Doppler ultrasound for adverse perinatal outcomes in low-income and middle-income countries: a systematic review.

OBJECTIVES: This systematic review examined available literature on the prognostic accuracy of Doppler ultrasound for adverse perinatal outcomes in low/middle-income countries (LMIC). DESIGN: We searched PubMed, Embase, Cochrane Library and Scopus from inception to April 2020. SETTING: Observational or interventional studies from LMICs. PARTICIPANTS: Singleton pregnancies of any risk profile. INTERVENTIONS: Umbilical artery (UA), middle cerebral artery (MCA), cerebroplacental ratio (CPR), uterine artery (UtA), fetal descending aorta (FDA), ductus venosus, umbilical vein and inferior vena cava. PRIMARY AND SECONDARY OUTCOME MEASURES: Perinatal death, stillbirth, neonatal death, expedited delivery for fetal distress, meconium-stained amniotic fluid, low birth weight, fetal growth restriction, admission to neonatal intensive care unit, neonatal acidosis, Apgar scores, preterm birth, fetal anaemia, respiratory distress syndrome, length of hospital stay, birth asphyxia and composite adverse perinatal outcomes (CAPO). RESULTS: We identified 2825 records, and 30 (including 4977 women) from Africa (40.0%, n=12), Asia (56.7%, n=17) and South America (3.3%, n=01) were included. Many individual studies reported associations and promising predictive values of UA Doppler for various adverse perinatal outcomes mostly in high-risk pregnancies, and moderate to high predictive values of MCA, CPR and UtA Dopplers for CAPO. A few studies suggested that the MCA and FDA may be potent predictors of fetal anaemia. No randomised clinical trial (RCT) was found. Most studies were of suboptimal quality, poorly powered and characterised by wide variations in outcome classifications, the timing for the Doppler tests and study populations. CONCLUSION: Local evidence to guide how antenatal Doppler ultrasound should be used in LMIC is lacking. Well-designed studies, preferably RCTs, are required. Standardisation of practice and classification of perinatal outcomes across countries, following the international standards, is imperative. PROSPERO REGISTRATION NUMBER: CRD42019128546

A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia.

In sub-Saharan Africans, maternal mortality is unacceptably high, with >400 deaths per 100,000 births compared with <10 deaths per 100,000 births in Europeans. One-third of the deaths are caused by pre-eclampsia, a syndrome arising from defective placentation. Controlling placentation are maternal natural killer (NK) cells that use killer-cell immunoglobulin-like receptor (KIR) to recognize the fetal HLA-C molecules on invading trophoblast. We analyzed genetic polymorphisms of maternal KIR and fetal HLA-C in 484 normal and 254 pre-eclamptic pregnancies at Mulago Hospital, Kampala, Uganda. The combination of maternal KIR AA genotypes and fetal HLA-C alleles encoding the C2 epitope associates with pre-eclampsia [P = 0.0318, odds ratio (OR) = 1.49]. The KIR genes associated with protection are located in centromeric KIR B regions that are unique to sub-Saharan African populations and contain the KIR2DS5 and KIR2DL1 genes (P = 0.0095, OR = 0.59). By contrast, telomeric KIR B genes protect Europeans against pre-eclampsia. Thus, different KIR B regions protect sub-Saharan Africans and Europeans from pre-eclampsia, whereas in both populations, the KIR AA genotype is a risk factor for the syndrome. These results emphasize the importance of undertaking genetic studies of pregnancy disorders in African populations with the potential to provide biological insights not available from studies restricted to European populations.This work was supported by the Wellcome Trust (090108/Z/09/Z, 085992/Z/08/Z, 089821/Z/09/Z), the British Heart Foundation (PG/ 09/077/27964), the Centre for Trophoblast Research at the University of Cambridge, a Wellcome Trust Uganda PhD Fellowship in Infection and Immunity held by Annettee Nakimuli, funded by a Wellcome Trust Strategic Award (084344), the US National Institutes of Health (AI017892), and the UK Medical Research Council (G0901682).This is the accepted manuscript of a paper published in PNAS (A Nakimuli, O Chazara, SE Hiby, L Farrell, S Tukwasibwe, J Jayaraman, JA Traherne, J Trowsdale, F Colucci, Emma Lougee, RW Vaughan, AM Elliott, J Byamugishaa, P Kaleebu, F Mirembe, N Nemat-Gorgani, P Parham, PJ Norman, A Moffett, PNAS 2015, 112, 845-850

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