How Pregnancy Affects a Lifetime of Health

How Pregnancy Affects a Lifetime of Health

Physiologists work to understand pregnancy-related conditions and later health issues.
By Marijke Vroomen Durning, RN

When people hear “women’s health,” they typically think of gynecological or obstetrical issues: pregnancy, postpartum, menstruation and menopause. While women’s health is much more than the reproductive organs, perhaps it is those reproductive-related conditions that may help researchers and clinicians begin to understand women’s health overall.

The Society of Maternal-Fetal Health Medicine calls pregnancy “a window to future health.” 
In fact, complications during pregnancy could have a negative effect as many as 50 years later, according to a 2023 article published in Circulation.

But pregnancy-related conditions and later health issues lead to the chicken-and-the-egg conundrum: Did the pregnancy cause the problem or was the problem already there? “There’s a school of thought that pregnancy itself is a stress test,” says Eric George, PhD, associate professor in the Department of Physiology and Biophysics at the University of Mississippi Medical Center. “That what it’s doing is unmasking undiagnosed, perhaps clinical, preexisting cardiovascular issues that are coming to the front because of the pregnancy.” 

Pregnancy-related complications such as preeclampsia, gestational hypertension and gestational diabetes could be early indicators of an individual’s later risk of cardiovascular disease. Other research shows that pregnant people who had gestational diabetes have a three-fold risk of developing metabolic syndrome later in life. Those who had preeclampsia have a two-fold risk of developing diabetes for 10 years following their pregnancy. They also have a higher risk of long-term kidney disease.

Researchers are diving deeper than ever into pregnancy-related complications to understand the mechanisms behind them. Through more research, clinicians could increase awareness, develop routine screening recommendations and create integrated care models to mitigate risks and promote better health outcomes.

“These complications put women on an accelerated trajectory for chronic disease across the lifespan, and we’re really interested in trying to understand why that is,” says Anna Stanhewicz, PhD, assistant professor of health and human physiology and director of the Microvascular Physiology Lab at the University of Iowa. “If we can study them during that time when they’ve recovered after the pregnancy, but before they develop disease, to understand what’s going on at the level of the blood vessel, it’ll give us an opportunity to intervene before they actually develop disease, with the goal of preventing it.”

Stanhewicz is motivated about her lab’s latest data, which showed that women who had a history of gestational diabetes had blood vessels later that were not as responsive to insulin. This is important because animal research shows that when blood vessels cannot respond appropriately to insulin, it predicts and precedes the development of systemic insulin resistance. “We’re excited about those data because we think it might be showing that this is a mechanism that’s contributing to the accelerated risk,” she says.

A Return to Basic Physiology

The basic physiological changes that occur during pregnancy is what Helen E. Collins, PhD, assistant professor of medicine at the University of Louisville, is focusing on in her mice studies.

In studying how the heart remodels during pregnancy, she says, “we found that during pregnancy and the early postpartum period, the heart is enlarged in size and that, contrary to some other publications that exist, we actually see this enlargement going as long as one year postpartum in our animal studies.” One year in a mouse’s life is equivalent to middle age in humans, which is significant when determining how this might affect people. 

Collins’ lab also saw a profound impact of lactation on the process, whereby some of this growth of the heart was almost instantaneously resolved when the mice were not experiencing active lactation. 

“Too often, heavy menstrual bleeding—which is far more common than recognized—is normalized by the patient, her family, society and health care professionals.”

Hilary Critchley, MD, DSc

“We have also performed studies where we looked at the impact of multiple successive pregnancies on heart growth,” Collins says. “We haven’t followed those out as far as one year yet, but what we do see is that there is always a pregnancy-associated cardiovascular growth response, but it’s comparable between successive pregnancy lactation cycles. It means there might be a set point at which the heart will grow to and [that] it won’t get bigger, rather than a cumulative response.”

Collins’ second study arm is looking into the impact of liver-heart communication, or inter-organ communication, during pregnancy. “We see in our pregnancy studies that liver-derived metabolites, such as ketone bodies, increase in circulation during pregnancy, but the physiological consequence of this is understudied.” Her grant focuses on examining the impact of ketone body metabolism on cardiac growth during pregnancy and the postpartum period.

“Hopefully upon completion of the study,” she says, “we’ll know not only the contribution of ketone bodies to metabolic remodeling in the context of physiological hypertrophy, but we’ll also have a greater understanding of whether our model could promote pregnancy-associated cardiovascular disease. We’ll know the contribution of that specific metabolic pathway to the disease progression, which could reveal future therapeutic targets.”

Anemia 

It is not uncommon for a female of childbearing age to be told she has anemia, but the issue goes deeper than that, says Hilary Critchley, MD, DSc, professor of reproductive medicine at the Institute for Regeneration and Repair in the Centre of Reproductive Health at the University of Edinburgh in Scotland.

The late manifestation of iron deficiency is anemia. “One of the problems we have—and why both iron deficiency and anemia are under-recognized and undertreated—is the patient, particularly at the time of pregnancy, will have her hemoglobin checked. The hemoglobin may be in the normal range as determined by the [World Health Organization] criteria, but unless you actually check a marker for iron deficiency you will not pick up that they are also iron deficient.”

The International Federation of Gynaecology and Obstetrics issued a position statement in September 2023 highlighting that anemia is under-recognized and undertreated. “It is present before pregnancy, during pregnancy and clearly gets worse as pregnancy progresses,” Critchley says. “It probably impacts more than 2 billion people worldwide and the predominantly affected are women, and during pregnancy there may be impacts on pregnancy outcomes, the developing fetus and infant.”

Clinicians should endeavor to identify and manage iron deficiency and iron-deficiency anemia, she says. “Too often, heavy menstrual bleeding—which is far more common than recognized—is normalized by the patient, her family, society and health care professionals. Women and reproductive-aged girls should be asked about their periods and menstrual bleeding experience.” Heavy menstrual bleeding can be addressed with often relatively simple, safe and effective interventions, she says.

The risk of preterm labor among pregnant people with iron deficiency is higher, as is the risk for severe postpartum hemorrhage and maternal death. “If your hemoglobin level is very low and you have a massive postpartum hemorrhage, you’re much more likely to die than if your hemoglobin is at a higher level,” Critchley says. “This is why detection and causes of anemia and iron deficiency prior to pregnancy, such as heavy menstrual bleeding, is a real public health message.”

Critchley also points out that when females are iron deficient, even with treatment, it can be difficult to get their levels back to normal, especially if they are menstruating and losing blood every month.

In addition to physical complications from iron-deficiency anemia during pregnancy, there can be a significant effect on mental health later. There is a strong association between isolated iron deficiency and postpartum depression, which affects up to 20% of new postpartum individuals. An estimated 5% continue to have high levels of depression for three years after delivery.

Preeclampsia 

An estimated 5% to 7% of pregnancies are affected by preeclampsia, resulting in 70,000 maternal and 500,000 fetal deaths worldwide. Preeclampsia is a pregnancy condition that can cause elevated blood pressure and high levels of protein in the urine. The exact cause is unknown, and the only “treatment” is to deliver the baby. Despite the belief that preeclampsia is resolved by delivery, some researchers think that the danger to the pregnant person doesn’t stop after delivery. 

George points out that many of the risk factors for preeclampsia are the same risk factors for cardiovascular disease, such as obesity and high cholesterol. “It’s a very complicated relationship,” he says. “But there is a very clear relationship, statistically, between women who have preeclampsia and what happens later.”

George’s lab has two projects in this area. One looks at the mechanisms that cause preeclampsia. “The prevailing wisdom about preeclampsia is that it’s an error in implantation and that’s causing inadequate blood flow to the placenta,” he explains. “In response to that, the placental tissue starts to malfunction and produces things that are secreted into the mother’s circulation, and that’s what causes all the downstream effects.”

The second project focuses on potential therapeutics for those with preeclampsia. Because the only “cure” is delivering the baby, babies are often delivered early, as early as 34 or 35 weeks of gestation. “Preeclampsia is the leading cause of prenatal birth,” George says. “There are epidemiological studies that show that those babies are going to have higher risk for all sorts of diseases throughout the rest of their lifespan.”

If researchers could find safe and effective treatment for preeclampsia, they could not only save lives during pregnancy, they could potentially prevent any long-term effects the preeclampsia might have caused in the child.

Mitochondria DNA

Styliani “Stella” Goulopoulou, PhD, associate professor of physiology at Loma Linda University School of Medicine in California, is looking at preeclampsia and future health from another angle: whether mitochondrial DNA in the circulation may be a potential biomarker for maternal vascular dysfunction.

“We’re interested in the biomarker potential of circulating mitochondrial DNA, but we’re also looking at mitochondrial DNA as a signaling molecule,” she says. Her lab team is working to find out how mitochondrial DNA circulates and varies during pregnancy, specifically in preeclampsia. They also want to know what type of cells mitochondrial DNA activates, how it affects the maternal vascular function and how it gets out of the cell in the first place. 

In 2022, the U.S. maternal death rate stood at 22.3 deaths per 100,000 live births, according to the CDC National Center for Health Statistics. Goulopoulou points out that while social issues play a role in this number, biology does as well.

“Pregnancy requires many physiological changes,” she says. “All maternal systems and organs change during pregnancy.” Then after delivery, everything shifts again and the female body has to make more changes. While this helps individuals meet the high metabolic demands of pregnancy, it also makes them vulnerable.

“If we could understand what factors shift healthy pregnancy adaptations to increased vulnerability for complications and find ways to target these factors, this would definitely reduce pregnancy complications and alleviate risk for future cardiovascular disease,” Goulopoulou says. 

Progress and Hope

When Collins gives talks about her research, she usually begins by saying that pregnancy, at least in the U.S., is dangerous. “But it doesn’t have to be if we increase awareness of the mere fact that women can have pregnancy-associated cardiovascular complications,” she says. “There have to be more people in the research arena that are looking at some of the key contributory factors. Also, we have to do a lot more in-depth mechanistic work to really elucidate those key physiological changes that occur in the heart during a normal pregnancy and disease-complicated pregnancy.”

Bringing this research to real life is the ultimate goal of these researchers. As females age and seek medical care, they might be asked about pregnancy history, including how many successful pregnancies they had. But rarely are they asked about health issues they experienced during pregnancy, such as hypertension. Given the long-term impact pregnancy has on a woman’s body, perhaps this should become routine practice. 

This article was originally published in the November 2024 issue of The Physiologist Magazine. Copyright © 2024 by the American Physiological Society. Send questions or comments to tphysmag@physiology.org.