Factors that trigger prematurity may be specific to a region or country

José Guilherme Cecatti

Professor titular de obstetrícia da Universidade Estadual de Campinas (Unicamp)
Project: Use of metabolomics for identification and validation of biomarkers for preterm birth

When it comes to forecasting events, humanity has come a long way. However, we are still unable to accurately assess whether a pregnant woman may have a spontaneous premature delivery, that is, before 37 weeks of gestation. Currently, there are only two ways to identify this risk: if a woman has had a premature baby before or if her cervix is ​​shorter than normal, under 25 millimeters.

The team, led by the obstetricians José Guilherme Cecatti, professor of obstetrics at the State University of Campinas (Unicamp) and Renato Souza (video), worked to develop an innovative way to predict prematurity by identifying biomarkers in the serum of pregnant women. The team tested different types of substances present in the body of pregnant women, resulting from metabolic processes in the body, to develop an algorithm capable of predicting the risks of premature birth with greater precision, something unprecedented globally. “In addition to the biomarkers, we also identified clinical factors, such as smoking and bleeding, and incorporated them into the algorithm,” says Cecatti.

Identifying women who are at a higher risk of premature birth allows medical professionals to adopt measures to prevent it during prenatal care. This could include, for example, administering medications, such as corticosteroids, to improve the maturity of the fetus’ lung, hormones, such as progesterone, and the insertion of the pessary, a silicone ring designed to decrease the possibility of a premature birth by closing the cervix. The information would also provide reassurance to low-risk, pregnant women, in addition to reducing public health expenses associated with prematurity.

Cecatti’s team was part of an international consortium called SCOPE (Screening of Pregnancy Endpoints) to understand common pregnancy complications, including spontaneous prematurity. The Brazilian study was based on an international study that tested the blood samples of almost 6,000 pregnant women taken at the 15th and 20th weeks of gestation for women from Auckland, New Zealand, and Cork, Ireland. The analysis used metabolomics techniques — the study of metabolites, substances and biological markers — to elucidate the mechanisms involved in spontaneous premature delivery. For example, researchers identified alkanes (compounds derived from paraffin) as associated with premature birth.

Using the same technology and methodology as in the international study, the research also collected blood and hair samples from 1,180 Brazilian pregnant women from Campinas, Botucatu, Porto Alegre, Recife and Fortaleza during the 20th week of pregnancy. Hair was collected because it may contain information (metabolites) that correspond to the woman’s metabolism and biological status, ranging from the period when they were collected to months prior, at the beginning of pregnancy or possibly even before. In addition, the hair strands do not need to be refrigerated and they do not require major requirements for conservation, which eliminates costs.

This collection had two objectives: to create a large biobank and to validate the results observed in international samples, identifying specific metabolites and substances present in pregnant Brazilian women, since some of them are related to the environment in which the women live. Now that they are collected, these substances could also be used in other studies involving the development of biomarkers for several other conditions identified during pregnancy.

The researchers followed each of these women to assess not only the occurrence of premature birth, but also the development of syndromes related to high blood pressure (pre-eclampsia), restrictions to fetal growth and gestational diabetes mellitus. Thus, it will be possible to investigate the factors related to the so-called “Great Obstetric Syndromes” in the Brazilian population.

One of the pregnant women who participated in the study: she was followed closely by the team until her baby was born

The study concluded that metabolites, biomarkers and other clinical factors related to prematurity vary significantly from country to country. In Cork, for example, substances resulting from the burning of fossil fuels such as long-chain hydrocarbons (dean and dodecane) are linked to premature birth, confirming and reinforcing the role of environmental pollution in triggering the prematurity. These findings were not present in New Zealand and Brazilian samples, for example.

“We believed that we would find the same pollutants, substances and exposure factors in the three contexts,” says Cecatti. “We were mistaken and, contrary to what we expected, the problem is caused by several factors and the probability of finding a single marker or few of them to predict the risk of premature childbirth is very small.” According to the team, biomarkers in pregnant women can change according to the population, life experience, type of environmental exposure, and region of the world.

In Brazil, the study has already identified markers that change according to the phenotype of the women, characteristics of an organism that vary according to the genes and the environment in which the woman lives. This means that the factors that lead to prematurity may change according to the body mass index (BMI), which measures whether a woman is obese or thin, and with ethnicity (black, indigenous). “Therefore, in a next phase, we intend to use the biobank to identify specific biomarkers and metabolites for the Brazilian context,” says Cecatti.

The clinical factors that can trigger birth before 37 weeks also change according to the country. Bleeding before 15 weeks of gestation and smoking during pregnancy were the only clinical factors associated with prematurity in Cork and Auckland. In Brazil, the only factor that was related with premature birth was a cervical length of less than 25mm. The research also identified the risk factors associated with other complications of childbirth, such as pre-eclampsia, fetal growth restrictions and gestational diabetes, which can also lead to prematurity.

Pregnant women who gain weight in an accelerated manner are more likely to develop high blood pressure during pregnancy (pre-eclampsia). Smoking is linked to slowed fetal growth and obesity, as measured by a higher BMI, is linked to gestational diabetes.