Study could help develop therapy to improve lung function in growth-restricted fetuses

If the fetus grows below normal during pregnancy, each week of gestation increases the risk that some of its organs may not develop properly, which can negatively affect the baby's health after birth. The long-term effects of restricted fetal growth on brain and cardiovascular development have been the subject of numerous studies, but there is a lack of scientific data on its effects on the lungs.

This was the subject of a study carried out jointly by the Center for Research in Fetal Medicine BCNatal (Clínic Barcelona and Sant Joan de Déu Hospitals) and the University of Pompeu Fabra (UPF), which revealed differences in lung development between growth-restricted fetuses and normal fetuses in terms of their vascular resistance. Researchers studied this by measuring the speed of blood flow in the fetus and analyzing this data with the support of artificial intelligence techniques and computer models.

The study, recently published in Scientific Reports, opens up the possibility of developing therapies aimed at improving lung development in growth-restricted fetuses and preventing respiratory problems. System that can continue not only in childhood, but also in adolescence and adulthood.

The lead investigators of this study are Fatima Crispiy, a BCNatal and Clínic-IDIBAPS researcher in the Fetal and Perinatal Medicine group, and Bart Bijnens (ICREA, UPF), a researcher in the BCN MedTech unit in the UPF Department of Engineering. The remaining researchers belong to various services and research groups of Clínic-IDIBAPS and are also associated with the University of Barcelona and CIBER for respiratory and rare diseases.

More than 200 pregnant women took part in the study. This study analyzed fetal blood flow and its changes with additional oxygen supply in 208 pregnant women from 24 to 37 weeks of pregnancy. All women were examined at the Clínic Hospital in Barcelona, where they underwent all the necessary tests for this study.

In 97 of these cases, the fetuses had limited growth restriction, resulting in very low birth weight. The remaining 111 fetuses had normal growth. In each of these fetuses, the blood flow velocity in the main arteries and pulmonary vessels was measured, then these data were compared using artificial intelligence. Additionally, lung resistance was calculated using a computer model.

Illustrative Doppler images of the main pulmonary artery and intrapulmonary artery of the fetus. Source: Vellvé, K., Garcia-Canadilla, P., Nogueira, M., et al.

The speed of blood flow in the lungs of the fetus was analyzed both under normal maternal breathing conditions and after additional oxygen supply through a mask (hyperoxygenation conditions). This analysis was carried out using a technique based on the emission of ultrasound waves to the fetus to estimate the speed of blood flow throughout its circulation based on Doppler principles.

In contrast, the resistance of organs such as the lungs cannot be measured directly using ultrasound, and a computer model representing the heart and blood vessels was used to measure it. For comparison, this computer model can be compared to a simulation of an electronic circuit. The researchers created a computer version of the fetal vascular system and, using measured blood flow rates and modeling other parameters, were able to estimate the resistance and elasticity of various organs.

In conclusion, machine learning methods based on artificial intelligence techniques were used to compare the blood flow patterns of fetuses, which helped group them into different categories according to flow parameters and clinical indicators.

Subsequently, consideration of the effects of hyperoxygenation showed that it was associated with changes in lung resistance as a result of additional oxygen supply to mothers, and more oxygen was shown to improve pulmonary blood flow in growth-restricted fetuses without affecting normal fetuses.

“Essentially, the study results show that growth-restricted fetuses have different mean blood flow rates as well as vascular resistance in the lungs than normal fetuses, and this can be normalized by providing supplemental oxygen to the mother,” explains Bijnens (ICREA, UPF).

"The discovery of these differences in the lung vasculature opens up the possibility of developing future therapeutic strategies to improve lung function in fetuses with growth restriction. After birth, these improvements in fetal development may reduce the risk of developing respiratory diseases later in life," explains Dr. Crispy (BCNatal, Clinic).