In Finland approximately 3,500 babies (roughly 5.5%) are born prematurely, i.e. prior to the 38th week of pregnancy. The risk of disease, permanent disability or death during the first week after birth is significantly higher for preterm babies than for those born at term.

One of the severe conditions in premature newborns is respiratory distress syndrome (RDS). At the beginning of the 1970s, more than 50 percent of the newborns suffering from RDS died. Almost all of these born before the 31^st week of pregnancy died. RDS was the most common cause of death for premature babies.

Today, almost all babies with RDS recover, and the mortality rate is less than five percent. Even babies born at the 23rd week of pregnancy can survive. These spectacular improvements have been seen during the thirty-year research career of Mikko Hallman, Professor in Pediatrics at the University of Oulu.

Hallman found a remedy for RDS from amniotic fluid. As early as in the 1950s, researchers had discovered that pulmonary alveoli remained open due to a compound called surfactant – without this surface-active agent human breathing would be impossible.

“When we studied maturation of fetal lungs we noticed that surfactant was secreted into amniotic fluid and that the composition of amniotic fluid corresponded to the developmental level of fetal lungs. When we noticed that surfactant was missing from the lungs already before birth, we started to ponder what to do. We decided to isolate the compound from full-term amniotic fluid and administer it to premature babies. Our very first therapeutic experiments showed that surfactant reduced mortality rate and also the incidence of pulmonary complication," says Hallman.

The therapy was taken into common use in the 1990s and it is routine clinical practice everywhere in the world, even in the developing countries. Current surfactant drugs that are derived from animal lungs may eventually be replaced by synthetic surfactants. Hallman, who has received several international awards, attained more valuable feedback on his work during the summer. As one of the 40 invited guests, he participated in a pediatric congress in the United States:

“When I had described our project on preterm birth, Mildred Stahlman, known as the founder of modern neonatology, stood up and stated with conviction that this type of investigation into the reasons behind preterm birth is the most important mission for those responsible for neonatal treatment today. That was great feedback.”

Even the placenta is not sufficiently known

One clear factor causing prematurity is an inflammation of the placenta and fetal membranes, but the ultimate reasons behind preterm birth are still unknown.

“We know surprisingly little about the function of the placenta during the third trimester of pregnancy. How to keep the placenta fully functional during the last few critical months of the pregnancy, this is the key to everything."

Additionally, the international prevalence of preterm birth is increasing. In the USA, approximately 13 percent of babies are born preterm, and in the black population the proportion is as high as 22 percent. Reasons behind this increase include multiple pregnancies, which increase the risk of prematurity; elsewhere in the world their incidence has increased due to in vitro fertilization.

According to Professor Hallman, research on this field should be intensified. The higher the number of full-term babies, the healthier the human race.

“It baffles me how little research on this topic is being conducted in the world. Prematurity reduces healthy life spans and weakens the quality of life, perhaps more than any other disease at the global scale,” ponders Hallman, making reference to cancer, for example.

Potential topic for a breakthrough in research

Currently, Hallman’s research group of 15 scientists is analyzing genes of women who have experienced spontaneous preterm delivery and genes of their immediate families. The study contains data on some families over a period of 35 years.

Researchers are calculating the probabilities of particular genes being involved in predisposition to preterm birth. Additionally, they also use an experimental animal model to test the significance of each candidate gene causing preterm delivery.

According to Professor Mikko Hallman, the University of Oulu provides excellent conditions for this research. Even internationally speaking, this research has a good framework in Finland.

“We have good pregnancy monitoring in Finland, and almost all high-risk deliveries are centralized at five university hospitals. Especially in Northern Finland, high-risk deliveries are well centralized in Oulu. Research work on this topic is easier to conduct here than in countries like the United States, where many children are born in small hospitals,” says Hallman who has more than ten years’ personal experience as a researcher at the University of California.

“In addition, in Finland, and in Eastern and Northern Finland in particular, we have a genetically homogeneous population. Furthermore, in Oulu and the surroundings, the birth rate is exceptionally high compared with other regions in Europe. Large families and minimal demographic variation essentially enhance the research on genetic factors causing predisposition to diseases. It has been shown that preterm delivery is influenced by the combined effect of maternal and fetal genetic factors. Large families in which some children have been born prematurely comprise a particularly convenient tool to study fetal genetic factors causing preterm labor. Hence, we are especially interested in families in which preterm labor recurs in several pregnancies. Naturally we will conduct follow-up studies to see if our results can be generalized in different populations.”

“Although our research is well supported, it really requires five times the amount of money we now have. We need to have a critical mass of excellent researchers in order to increase the probability of a breakthrough. If we think of potential fields for breakthrough research, this is one of them.”

Information transferred beyond borders

Recently, Hallman’s research group received a grant for a project in which eight European research centers will participate. Thanks to the project, researchers in Oulu will receive a lot of new research material from the gene banks of their partners.

The group collaborates with local investigators and with some leading geneticists from Finnish Genome Center, Sanger Institute and from some US Centers.

The researchers have utilized CSC’s supercomputer by searching for common links between the prematurely born child and the protein concentrations and gene variants associated with preterm delivery. Two hundred neonates born prematurely over a four-year period are participating in the study, and they are currently in their 9^th year of follow-up. Extensive clinical data, ranging from the placenta to the brain, has been collected from deliveries.

“Having access to the supercomputer has enhanced our large-cohort analysis, for the number of parameters is immense, sometimes even hundreds of thousands,” says Hallman in gratitude to CSC. He is happy with the collaboration with CSC that has continued for almost ten years.

Image: During the thirty years of research conducted by Professor of Pediatrics Mikko Hallman, RDS mortality rate has dropped from over 50 percent to less than 5 percent. © Onni Kinnunen / Studio P.S.V.

Raija Tuominen