Digital atlas records the ideal evolution of the brain during pregnancy – 01/14/2024 – Science

High-resolution ultrasound images of 899 babies have allowed an international group of researchers to accurately map the development of the brain and other portions of the brain of healthy children in the womb. Gathered in a digital atlas available on the internet, the result of this work should serve as a reference for what would be the expected and desirable evolution of the brain during pregnancy. It should also help doctors identify early injuries or problems with neurological maturation that could lead to future harm. The study was carried out under the coordination of obstetrician José Villar and human reproduction specialist Stephen Kennedy, both from the University of Oxford, in the United Kingdom, with the participation of Brazilian researchers, and published in October in the journal Nature.

To arrive at the parameters of what appears to be the optimal development of the human brain in the mother’s womb, almost 200 researchers monitored the pregnancies of 899 women in eight countries — including Brazil — from 2009 to 2016 in the Americas, Europe, Asia and Europe. Africa. The specialists carried out three-dimensional ultrasound examinations of the fetus periodically, from the 14th week of pregnancy until close to delivery, always using the same type of equipment and standardized procedures, which made it possible to reconstruct the evolution of the brain week by week. All mothers were in good health and had the highest educational level in their communities. None smoked or had illnesses that could compromise the baby’s development.

The reason for choosing this group is that women with more years of education tend to take better care of their own health and are at less risk of experiencing problems during pregnancy. And only the monitoring of fetuses gestated in the best conditions allows us to know what would be the supposedly ideal evolution of the structures of the brain and other parts of the brain.

“Our atlas fills a six-week knowledge gap in understanding how the brain matures early in fetal life,” said Ana Namburete, a researcher at the University of Oxford and first author of the study, in a press release. “We also revealed significant asymmetries in brain maturation, such as in the region associated with language development, which peaked between 20 and 26 weeks of gestation and persisted without differences between the sexes,” she said.

Measuring fetal brain structures is not simple. From the 14th to the 31st week of pregnancy, the period detailed in the current atlas, the total volume of the brain grows 13 times, from 24 cubic millimeters (mm³) to 318 mm³. In this phase, there is intense proliferation of cells and the establishment of connections between them, in addition to the migration of cell groups to specific regions, which will form control nuclei for different functions. “Errors in neuronal proliferation can occur during this period, capable of leading to clinical consequences”, explains neuroscientist Andrea Jackowski, from the Federal University of São Paulo (Unifesp), who studies brain development, but did not participate in this study. “These are times when the brain is more vulnerable to the influence of environmental factors and any form of aggression can have repercussions for the child later. But this stage can also act as a window of opportunity to intervene and solve problems”, she says.

Asymmetries

Another factor that makes measurements difficult is that during this period the right and left hemispheres are beginning to become asymmetrical, with some regions gaining more volume in one than the other. This means that it is in the womb that the brain assumes the configuration it will have for the rest of life, even if it is not completely mature and undergoes changes later on. “It is a fundamental phase of maturation, in which, after initial formation, the processes of specialization and regional development of brain structures occur. It creates the foundation so that babies, when born, are ready for their first acts of cognitive development” , says psychiatrist Pedro Pan, also from Unifesp, who did not collaborate with the Nature work.

Added to these transformations is the fact that the fetus moves a lot in the uterus, which complicates obtaining images, which in the current study were improved with the help of artificial intelligence. “The authors had to use machine learning techniques and deep neural networks, in addition to complex image processing methods, to be able to build the atlas”, says statistician and neuroscientist João Ricardo Sato, from the Federal University of ABC (UFABC), who evaluated the study at the request of Pesquisa FAPESP.

Several groups had already recorded the brain development of human fetuses, but they covered a later period (from the 19th week of gestation) and were carried out with fewer participants (from 12 to 197) — almost always attended at a single center and not monitored. after birth.

The work published in Nature included pregnant women of different ethnicities and followed the children until their second year of life. It is part of the International Consortium on Fetal and Newborn Growth for the 21st Century (Intergrowth-21st), which followed almost 20,500 children from pregnancy to the first years of life and allowed the production of intrauterine life growth curves at 2 years (see Pesquisa FAPESP nº 225).

“This is the largest study, to our knowledge, that describes the early normative development of the human brain,” the authors of the Nature paper wrote. “Our fetal brain reconstructions provide the first in vivo representation of the entire second trimester [da gravidez]”, they stated.

“The material provides a normal pattern of fetal brain growth, which is important for diagnosing neurological problems at this stage of life”, explains pediatrician and epidemiologist Fernando Barros, from the Federal University of Pelotas (UFPel), co-author of the study. from Nature and coordinator of Brazilian participation in Intergrowth-21st, who contributed images of 86 fetuses for the study. “The atlas can become a valuable tool for health professionals, helping with clinical decision-making and prenatal care, as well as being useful for teaching,” he says.

“Ultrasound exams usually carried out allow us to identify problems from the 22nd week of pregnancy. With the development pattern presented in the atlas, it may be possible to detect changes earlier”, concludes obstetrician specialist in fetal surgery Denise Lapa, from Hospital Israelita Albert Einstein, in São Paulo.

Scientific article
NAMBURETE, AIL et al. Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years. Nature. 25 Oct. 2023.