How does immune system change during pregnancy?

Using a novel method, scientists identified the blueprint of adaptive and innate immune modifications throughout gestation and beyond.

From cravings to morning sickness and hormonal swings, pregnancy certainly ushers in a barrage of physical changes at every level. Most have been explored already, but what about immunity?

Although scientists knew that a pregnant woman’s immune system makes adjustments, the scope and timing of these changes remained a mystery. Now, researchers have mapped how the immune system adapts systemically throughout pregnancy, providing a baseline for normal development that may clarify why some women’s bodies do not respond in expected ways, increasing their risk of preterm labor and complications.

“To understand the timing of immunological changes during pregnancy, we needed to frame the analysis completely agnostic to trimester,” explained senior author Brice Gaudilliere from Stanford University.

By framing gestational age as a continuous variable, the team devised a method for predicting how immune cells change by converging blood cell analyses with statistical modeling.

“Many studies indirectly collect information via cytokine or proteomic levels,” said Gaudilliere. “Actual immune changes in pregnancy couldn’t be assessed before the advent of our tool—CyTOF—which merges traditional flow cytometry with mass spectrometry.”

The Stanford team drew blood samples from 18 women with during their pregnancies—once during each trimester and a fourth time 6 weeks after delivery. Employing CyTOF—a flow cytometry method using antibodies labeled with heavy metal ion tags instead of fluorophores—they simultaneously measured up to 50 properties for each of the millions of immune cells they extracted, identifying 984 immune features and 24 cell subsets.

Interestingly, the researchers observed a drop in molecular signals that promoted anti-fetal immune responses during early pregnancy and enhanced antibacterial and antiviral immunity throughout all trimesters. Mid to late pregnancy also showed increased neutrophil numbers and expanding peripheral regulatory T cells. Postpartum samples suggested immunological recovery and higher maternal tolerance to fetal cell implants.

“This study clearly shows immunological changes in pregnancy are dynamic, not monolithic,” commented Gil Mor from Yale University, who was not involved with the present research. “Pregnancy is its own immunological state, with the immune system playing certain roles at different times.”

These findings may one day help physicians predict both term and preterm birth. Since inflammatory responses may trigger early labor, Gaudilliere anticipates that future blood tests could detect immune signals of impending delivery.