New Test Measures Preterm Infant Immunity Using Only Two Drops of Blood

Preterm infants are particularly vulnerable due to their organs still undergoing development, which can lead to difficulties in breathing, eating, and regulating body temperature. This is especially true for infants born as early as six to seven months of pregnancy, known as extremely preterm infants. These infants essentially continue their development outside the womb, facing even greater risks. Research in this population is complicated because conventional tests, such as blood draws, can be life-threatening due to the limited blood supply in these tiny patients. Now, a new methodology, combined with advanced techniques that analyze multiple molecular markers, is enabling researchers to gain valuable insights into the immune systems of extremely preterm infants more safely.

Researchers believe that early exposures to infections and environmental factors play a crucial role in shaping immune function later in life, though the exact impact of premature birth on the immune system is still under investigation. It was once thought that infant immune systems were not fully mature at birth, but accumulating evidence suggests that full-term babies are born with functioning immune systems, albeit different from those of adults. For preterm infants, determining whether this is also true has been challenging. Immune system studies typically require blood samples, and standard research methods use between 10 to 50 milliliters of blood. Collecting that amount from preterm infants could be harmful, draining their blood supply. Now, with only two drops of blood, researchers at Yale School of Medicine (YSM, New Haven, CT, USA) have demonstrated that preterm babies possess unique immune systems capable of responding to threats both before and after birth. This research, published in Science Translational Medicine, marks a key step in understanding the immune systems of extremely preterm infants, which is vital for improving care for this vulnerable group.

In their study, YSM researchers combined a protocol developed by Swedish researchers with advanced molecular techniques, enabling them to gather substantial data from just two drops of blood. Collaborating with Yale’s NOURISH team, the researchers collected blood samples from 10 extremely preterm infants, ranging from their first week to two months of age. They then analyzed protein expression and cell types in these samples, comparing them to data from adults and full-term infants. The results showed that preterm infants have a full array of immune cells, similar to those in adults and full-term infants. These babies even had memory T and B cells, which the immune system uses to recognize and respond to previously encountered threats. This finding suggests that these preterm infants were not only reacting to environmental exposures but may have also developed immunity while still in the womb.

However, the development of immune cells in preterm infants differed from that in full-term infants. The researchers observed that protein pathways and cell types related to inflammation were more active in extremely preterm infants, and this inflammation persisted for a longer period than in full-term infants. Around half of the preterm infants in the study had been exposed to an infection in the placenta before birth. These infants showed even higher levels of inflammatory cells in their blood than those who had not been exposed to such an infection. The long-term implications of these findings for the health of preterm infants remain unclear. While large-scale epidemiological studies suggest that early life exposure to pathogens and other immune triggers may increase the risk of conditions like asthma and irritable bowel syndrome, some early exposures also seem to protect against diseases like diabetes.

Though this small cohort has not yet provided enough data to establish definitive links, the researchers hope to shed more light on these potential connections. The team has now expanded their study to include around 250 preterm infants and is recruiting a comparable group of full-term infants for long-term observation, with plans to follow these infants for at least a year. They are also beginning to collect additional samples, including stool, skin, and nasal swabs, to further explore the development of the immune system in early life. The researchers remain optimistic about their findings and reassure parents that even preterm infants have the ability to combat infections and develop immunity despite arriving early into the world.

“The more premature an infant is, the more complications there are,” said Liza Konnikova, MD, PhD, an associate professor of pediatrics, immunobiology, and reproductive sciences at YSM and senior author of the study. “Our goal is to determine how long early-exposure impacts last, and whether they change your risk one way or another.”

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