Awards
Grand Challenges is a family of initiatives fostering innovation to solve key global health and development problems. Each initiative is an experiment in the use of challenges to focus innovation on making an impact. Individual challenges address some of the same problems, but from differing perspectives.
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A Randomized Clinical Trial with Oral Magnesium Supplementation in Pregnancy
Joao Guilherme Bezerra Alves from the Instituto de Medicina Integral Professor Fernando Figueira in Brazil will perform a randomized controlled trial to assess whether a daily oral supplement of magnesium citrate can prevent placental vascular disease, which can lead to preterm birth. Placental vascular disease restricts the flow of nutrients to the fetus and can cause growth restriction and maternal hypertensive disorders. Magnesium is known to promote placental vascular flow, and magnesium citrate is safe, inexpensive and easily absorbed in the body. They will perform a clinical trial in two large hospitals in Brazil in which 3,000 pregnant women will be offered a daily magnesium supplement or a placebo control starting from up to 20 weeks of gestation and continuing until birth. The effect on various outcomes including placental function, preterm labor, and mother and child health will be evaluated.
ABC Transporters in Pregnancy and Preterm Labor
Tania Maria Ruffoni Ortiga from the Universidade Federal do Rio de Janeiro in Brazil will measure the levels of so-called ABC transporters throughout pregnancy, and during normal and preterm labor, and how they are influenced by infections such as malaria and influenza, to determine whether they might increase the risk of preterm labor. ABC transporters sit in the outer membranes of cells and actively transport drugs, toxins and immune signaling molecules out of them. In this way, they regulate the immune response, hormonal signaling and the activity of drugs such as antibiotics, which become particularly important during pregnancy and labor. They will collect human intrauterine tissue at different time points during pregnancy and during cesarean delivery from hospitals in Brazil and Canada, and investigate the distribution of ABC transporters and the association with infection. They will also use a mouse model of malaria to evaluate the effect on the levels and activity of the transporters.
Association Among Fetal Microbiota, Prematurity and Preterm Morbidities
Renato Soibelmann Procianoy from the Universidade Federal do Rio Grande do Sul in Brazil will analyze the association between bacterial populations in the vagina and gut of mothers in their third trimester and in the meconium of very preterm newborns, with risk of preterm delivery. It was previously assumed that microbes from the mother are first transferred to the fetus during delivery. However, it was recently shown that this could happen already in the uterus, triggering a possible immune response by the fetus that may lead to premature birth, which is a leading cause of infant morbidity and mortality. They will use 16S rRNA-based bacterial sequencing technology on around 600 samples to compare the types of bacteria present in preterm infants with that in healthy term infants in a neonatal unit in the Clinicas Hospital in Porto Alegre. They will also track the changes in bacterial composition in healthy and sick newborns during their hospital stay, to identify types of bacteria associated with specific diseases such as diarrhea. All samples will be stored in a repository for future case-controlled studies.
Breastfeeding in Premature Infants: Impact of Bfhi in Neonatal Units
Carmen Gracinda Silvan Scochi from the Universidade de São Paulo in Brazil will encourage mothers of preterm infants in Brazil to exclusively breastfeed them for the first six months to better protect them against infections and optimize their growth and neurodevelopment. The incidence of preterm births in Brazil is increasing, and causes multiple short and long-term complications. Exclusive breastfeeding can limit some of these complications but is particularly challenging with preterm infants due to their incomplete development and the need for hospitalization, as well as there being practical and emotional difficulties for the mother. The existing WHO/UNICEF global program for promoting exclusive breastfeeding has been adapted specifically for preterm infants and involves better educating medical staff so that they provide the practical and emotional support to encourage exclusive breastfeeding. They will establish the program in 10 hospitals/maternity units across Brazil and evaluate its effect on the numbers of preterm infants being exclusively breastfed.
Elaboration of a Lyophilized Human Milk Concentrate To Be Used To Feed Very Low Birth Weight Preterm Newborns
Jose Simon Camelo Junior from the Universidade Federal de São Paulo in Brazil will test a method for producing a lyophilized human milk concentrate for feeding very low birth weight newborns that can be implemented in developing countries. Very small premature babies of less than 1,500 grams require large quantities of proteins, calories, minerals, micronutrients and electrolytes to survive and thrive. However, breast milk alone is not concentrated enough. Supplements derived from cow's milk have been used but appear to inhibit particularly the immunological quality of human breast milk, which helps block infection. Human milk additives have now also been tested and show promising results, but they are prohibitively expensive to produce in developing countries. They will use a simple method involving evaporation, centrifugation and lyophilization to produce a concentrated form of human milk that can be implemented in Brazilian milk banks. The milk product will be evaluated for stability and safety and for nutritional content to ensure it contains adequate concentrations of essential nutrients within manageable volumes to support very low weight newborns.
Improved Method of Screening for Preeclampsia
Renato Luis da Silveira Ximenes of Universidade Federal de São Paulo in Brazil will conduct a randomized controlled trial to evaluate whether a daily low dose of aspirin taken from early in pregnancy can prevent preeclampsia and thereby reduce the rate of preterm birth. Preterm birth is a leading cause of neonatal morbidity and mortality, and preeclampsia is a major cause of maternal death. The combination of several biomarkers such as serum levels of placental growth factor and biophysical measurements such as mean arterial pressure can now quite well identify women at higher risk of developing preeclampsia already at 11-14 weeks gestation, providing an early window of opportunity to treat them. And a recent meta-analysis suggested that the administration of low dose aspirin before 16 weeks could reduce the rate of preeclampsia by fifty percent. They hypothesize that the earlier treatment is started, the more effective it will be. They will screen pregnant Brazilian women at 11-14 weeks to identify those at risk of developing early preeclampsia and test whether low dose aspirin can prevent it.
Influence of the Vaginal Microbiome and Vaginal Metabolites on Cervical Remodeling and Preterm Parturition
Antonio Fernandes Moron from the Universidade Federal de São Paulo in Brazil will investigate whether the presence of specific bacterial populations in the vagina can predict preterm birth, which could form part of an inexpensive test suitable for low resource settings. Preterm birth leads to major short- and long-term health problems for the child. The causes are largely unknown, making it hard to identify pregnant women at increased risk who need monitoring and might benefit from treatment. They hypothesize that bacterial infections in the vagina during pregnancy can alter the length, elasticity and/or thickness of the cervix, thereby triggering preterm birth. To test this, they will analyze vaginal samples from 400 pregnant women located at four urban care centers throughout Brazil to identify bacteria and selected proteins that associate with specific cervical alterations detectable by ultrasound, and determine their association with preterm birth.
Pessary Plus Progesterone to Prevent Preterm Delivery in Women with Short Cervical Length
Rodolfo de Carvalho Pacagnella from the Universidade Estadual de Campinas in Brazil will perform two randomized clinical trials across 15 obstetric clinics in Brazil to evaluate treatment with progesterone in the presence or absence of a cervical pessary for preventing spontaneous preterm birth. Both cervical pessary and progesterone are individually considered to be effective preventative treatments for preterm birth, which is one of the most common complications seen in pregnancy and can cause severe complications for the premature infant. The causes of preterm birth are mostly unknown, although incidence does increase with cervical shortening during the mid stages of pregnancy. They will also analyze the prevalence of a short cervix in Brazilian pregnant women, and determine how well it predicts preterm birth. Their approach to screen for cervix length and then treat high-risk individuals with the combination therapy will also be evaluated for cost-effectiveness.
Premature Births in São Paulo: A Spatial Approach
Silvia Regina Dias Medici Saldiva from the Instituto de Saúde in Brazil will determine whether and which physical, social and cultural aspects of urban environments can increase the incidence of preterm birth. Prematurity is a major cause of childhood mortality and disability, and levels are high in Brazil. Preterm birth is likely caused by combinations of factors that, particularly in urban locales, might include environmental factors such as the quality of housing, proximity to health facilities and pollution levels, which then interact with social and cultural factors. They will identify spatial clusters of premature births from 2012 in the city of São Paulo to define suitable regions for performing case-control studies. The studies will involve face-to-face interviews at selected households by trained interviewers to assess environmental and social factors such as income, education, health and sanitation. These data will be supplemented with available or modeled meterological and pollutant data, and data from tree rings, which can provide climate information as well as levels of toxins. They will then perform hierarchical modeling to identify environmental factors associated with preterm births.
Quarenta Semana: Innovative Intervention in the Prenatal Care for Reduction of Prematurity
Jose Maria de Andrade Lopes of the Instituto Fernandes Figueira - Fiocruz in Brazil will conduct a randomized study to evaluate "Quarenta Semana," which is a program designed to remove risk factors associated with preterm births in Rio de Janeiro. The preterm birth rate in Brazil is amongst the highest globally. Some known risk factors for preterm birth include limited access to healthcare services, maternal social and health factors such as diabetes, and the quality of prenatal care. They will train pregnant women to act as health advocates who encourage women to seek prenatal care in their first trimester. They will also establish social support groups to help reduce stress and offer support throughout pregnancy, and implement a checklist for providers and patients to increase the quality of prenatal care. The effect of these approaches on preterm birth rates will be evaluated.