Two major studies coordinated by Unicamp's Tocogynecology Department (DTG) in the area of maternal and child health are promoting a true journey against prematurity in the country: the Preterm Samba and MAES projects. Funded by the Bill & Melinda Gates Foundation and Fapesp, they are part of the Brazilian Network for Studies in Reproductive and Perinatal Health. The initiatives seek to understand the best ways to prevent premature birth nationally, detecting and early monitoring women who are at high risk for premature birth, in order to carry out interventions. “It is estimated that, for every ten births in Brazil, one is premature”, revealed obstetrician José Guilherme Cecatti, responsible for the two studies.
Organizers of these projects are already celebrating the final phase of data analysis from the Preterm Samba project and the initial phase of the Maternal Actigraphy Exploratory Study (MAES) project, whose title in Portuguese is Exploratory Study of Maternal Actigraphy. The network brings together research for proposition and implementation, with as much information and cases as possible to evaluate and generate scientific evidence related to the topic.
In addition to addressing biomarkers that predict gestational risk, they also discuss information from all women who have had premature birth, pre-eclampsia, fetal growth restriction, and gestational diabetes. “We planned an analysis of all conditions and risk situations that could characterize a greater probability of developing one of these conditions”, informed Cecatti.
DTG presented the two studies in the Grandes Desafios Brasil: Prevention and Management of Premature Births program, which proposes investing in research to understand the causes of premature births and offer innovative solutions to reduce them. More than 850 researchers from 50 countries are part of the group of innovators who have been funded by the Bill & Melinda Gates Foundation since 2008.
Samba
The first study by the Unicamp group (Preterm Samba), proposed by Cecatti, was one of the winners of the Grand Challenges Explorations, a program in partnership with the Universities of Auckland-New Zealand and Leicester-United Kingdom. He intends to find, among women pregnant for the first time and at low gestational risk, biomarkers with the help of metabolomics, a technique that quantifies the metabolites produced or modified by the organism. The goal is to early detect women at high risk for premature birth in order to reduce it.
The project has already been implemented in five Brazilian universities (Campinas-Unicamp, Botucatu-Unesp, Federal University of Rio Grande do Sul-Porto Alegre, Federal University of Pernambuco-Recife and Federal University of Ceará-Fortaleza).
Women are invited to participate in the study and have their data entered and monitored on an online platform. A multidisciplinary team collects information in a standardized way. Blood and hair from the participants are also collected, biological samples that make up the first Brazilian biobank of low-risk pregnant women installed at the Women's Hospital and which follow international standards from the Scope reference study.
At this time, the study's international partners in England are carrying out metabolomic analyzes that will help arrive at biomarkers. They will be tested against samples from all women who participated in the study and whether or not they had premature births. The intention is to observe whether these biomarkers will in fact identify women at risk for premature birth.
Actigraphy
The second study (MAES) will examine whether physical activity and sleep/wake patterns will influence the health conditions of pregnant women. Changes during pregnancy, similar to what has already been demonstrated in other situations outside of pregnancy, suggested that sleep or physical activity patterns may be early associated with the onset of diseases that, if appropriately identified, could be potential predictive conditions, alerting the team of health about a pathology before it takes hold.
Cecatti believes that studying this condition exploratoryly would be a way to monitor who is at greater risk of developing, for example, pre-eclampsia (which is hypertension associated with pregnancy), in the case of a woman who is pregnant and undergoing prenatal care.
MAES integrates a call from the Gates Foundation called “Wearable technologies”, “wearable” computer technologies, which can be used in a simple way and without compromising the user's activities. This technology uses an actigraph, a type of digital watch that the pregnant woman places on her wrist, which estimates and monitors, among other factors, changes in sleep and physical activity.
This watch will initially be tested on around 400 pregnant women to identify normal patterns of physical activity and sleep during pregnancy, as well as patterns linked to serious medical conditions. This will record information about your physical activity, as well as sleep characteristics, waking activities and types of sleep activities related to complications during pregnancy.
The actigraph helps observe early signs of serious medical conditions, such as gestational diabetes and premature birth, so they can be recognized early, treated or even prevented. To measure activities, different algorithms based on bioinformatics will be developed. “We will start with the inclusion of cases and the import of devices from England”, he reported.
Cecatti recalled that some chronic diseases such as diabetes and cancer are known today to be associated with sleep disorders and physical activity. Therefore, the group will study whether this is also the case for complications during pregnancy.
Ideally, women should wear the watch during the second half of pregnancy (from the fifth month until delivery) and that it should be connected to a computer at each appointment. Thus, the information recorded about physical activity and sleep will be retrieved and specific software will analyze the patterns with the information obtained.
“Firstly, a standard of normality for pregnant women will be obtained, which does not yet exist, and then a differential will be established to compare women who will later develop premature birth, diabetes and pre-eclampsia”, commented the obstetrician. “We will investigate whether they have a different pattern from those who do not have any problems, being able to predict those who show a greater risk.”
Grand Challenges
Grand Challenges Explorations is a program characterized by an exploration phase, with funding of US$100 thousand, which presupposes a complement from Fapesp, with a similar amount. When the first phase is implemented and is promising for maternal and child health, proponents compete for the second phase.
With the knowledge acquired in the first, a larger study is proposed, with a greater number of cases and a greater number of participating centers. It is then possible to obtain financing of up to US$2 million.
Cecatti predicts that, by the end of 2019, MAES will be completed and that, if successful, it could lead to the second phase of the project, which is its application. A survey previously carried out by the Unicamp group, on prospective surveillance of severe maternal morbidity, included 27 participating centers and 60 researchers. Almost 84 thousand births were monitored and information was obtained on morbidity occurrences for almost ten thousand women. “Such information collected was fundamental for understanding the occurrence of severe maternal morbidity in the Brazilian context and, in the same way, it is believed that the SAMBA and MAES studies could bring valuable data to the study of maternal complications.”
The expectation is that the result of the SAMBA project will identify a set of useful markers for practical clinical activities and that the MAES project will shed light on the identification of a specific pattern of physical activity and sleep in the women evaluated, managing to predict those at greater risk. “Only then will we be able to recommend some type of intervention, through public policies, with support from the Ministry of Health and the World Health Organization (WHO)”, she commented.
