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Pregnancy is a miraculously odd state of existence. In mere months, the body grows an entirely new and temporary organ (the placenta), not to mention a new person.

It makes about  as normal and breathes . It also starts giving a visceral “nope” to foods and smells that were innocuous (even the universally lauded  can send a pregnant woman reeling). But these aversions don’t merely turn the stomach. They may point to an undercurrent of changes in something that has seemingly nothing to do with brewed beans: the immune system.

From Yum to Yuck

Researchers  in a cohort of 58 women that those with food and odor aversions in their first trimester of pregnancy (with meat and tobacco smoke being the most common) had higher levels of pro-inflammatory cytokines in their blood than those without. Modest levels of nausea and vomiting during pregnancy are correlated with positive birth outcomes. Aversions are hypothesized to be a behavioral response that prevents women from eating foods containing potentially harmful compounds or pathogens, or hanging around toxic substances.  

These findings suggest there may be an immunomodulatory component to such reactions. While the mechanisms behind this association are unknown, the work touches on something that is very clear—shifts in the immune system are integral to the machinations and outcomes of pregnancy.

Pregnancy and the Immune System

The immune system’s job is to protect the body from foreign invaders, like microbial pathogens. An embryo—half of whose cells and DNA are foreign to a woman’s body—thus poses an interesting conundrum. The immune system must calibrate in such a way to maintain its defenses without rejecting the developing fetus.  

There is no single set of changes that happen at the beginning of pregnancy and carry through to the end. Rather, immunological alterations are precisely timed throughout pregnancy (an , if you will). Some of these immunological fluctuations are well-established. For instance, early pregnancy is characterized by a ; the inflammation they ignite in the uterus supports embryogenesis by, among other mechanisms, inducing expression of adhesion molecules on the tissue surface.

This could be where food and odor aversions tie in.  observed in women with food and odor aversions point to an immune state associated with better implantation and placenta formation; lower levels, seen in those reporting no food or odor aversions, could indicate a risk or be a marker for unsuccessful implantation. Additional investigation is needed to see if that’s the case; why and how aversions and inflammation are linked also warrant further study. But, generally, if certain components of the pregnancy immune clock are missed or wonky, it may predispose to adverse pregnancy events.
 
This early inflammatory landscape is temporary. After placental implantation, the Th1 wave is , which orchestrate the tamping down of responses that could lead to fetal rejection or pose a risk to the fetus (e.g., inflammation, while necessary at the very beginning of pregnancy, can  later on). Toward the end of pregnancy, inflammation bubbles up again, stimulating the uterus to prepare for birth.  

Other cells hailing from both the innate (e.g., ) and adaptive immune responses wax and wane throughout pregnancy, too. This network of pregnancy immune responses is regulated by a broader web of interacting factors. For instance,  in mice showed that metabolites produced by the maternal gut microbiota (specifically those derived from the amino acid tryptophan) promote the emergence of regulatory immune cells that balance pro-inflammatory cellular responses at the maternal-fetal interface. This regulation, in turn, facilitates tolerance of the fetus and supports fetal development.  

Hormones like  also influence immune responses by, in part, binding to immune cells and suppressing their functions and controlling the expansion of certain cell subsets (e.g., regulatory T cells). Moreover, encapsulated in the placenta——the developing fetus produces molecules that can modulate maternal immune responses (e.g.,  of innate immune cells).

Increased Infection Susceptibility and Severity

But there’s a catch to all this immunological reorientation (apart from its purported ties to nausea and vomiting). Except for the very beginning and end of pregnancy, a woman’s immune system exists in a largely suppressed state. It’s ; it just works differently. The downside is that pregnancy increases susceptibility and/or severity of certain infections. 

Urinary Tract Infections

For instance, urinary tract infections (UTIs) are one of the most common infections among pregnant women.  during pregnancy can limit the ability of the bladder to empty completely, creating an environment that supports bacterial growth, and immune changes impair the body’s ability to eliminate the bacteria effectively.

 

Listeria monocytogenes Infection

The same problem crops up for infections in other body sites, too. It is well-known that pregnant women are  from the intracellular pathogen Listeria monocytogenes (hence the guidance to avoid lunch meat and other foods in which the bacterium is commonly found). Clearance of this and other intracellular pathogens, , requires a strong . Given this response is reduced during a pregnancy, those pathogens may have a better time evading host responses. L. monocytogenes also expresses molecules that allow it to easily cross the placenta, posing a threat to the fetus.

Malaria

In some cases, the immune system shifts in pregnancy don’t necessarily increase the risk of infection, but they do increase disease  severity upon infection. Pregnant women are , in part, due to the suppressed state of their immune system. Moreover, Plasmodium falciparium, , can infect the placenta and negatively impact its function and fetal development.  

In other words, the very changes that make pregnancy possible are the same ones that leave openings for microbes that might normally be stopped (or at least prevented from doing their worst).

The Good News

For this reason, it is advised that pregnant women take steps to minimize their risk of getting sick. The good news is there are ways to shore up defenses against common infections, with vaccines being key. , like those for flu, whooping cough, COVID-19 and respiratory syncytial virus (RSV), among others, are safe and recommended by doctors for pregnant individuals. , managing symptoms  (a sign of robust immune activity) are important for both maternal and fetal health.  

And, of course, it pays to heed one’s food or odor aversions—they may be doing some of the work, too. 

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Like pregnant women, the immune systems of babies are fine-tuned to a specific stage of life. Research suggests the infant immune system isn’t “immature,” it’s just regulated differently than that of adults. This conceptual shift could shape neonatal infection prevention and care.