A recent study led by Duke University researchers finds that women with Systemic Lupus Erythematosus (SLE), also known as lupus, face a much higher risk of developing preeclampsia, a disorder that causes high blood pressure during pregnancy, than those with other rheumatic diseases and those without them entirely.
“We know that pregnancy outcomes, primarily preeclampsia, in women with lupus are much worse than the general population and women with other rheumatic diseases. What has not been well studied before was the impact on infants.” said Amanda Eudy, PhD, assistant professor in the Division of Rheumatology in the Duke Department of Medicine. Eudy served as the epidemiologist for the study.
Preeclampsia can lead to preterm delivery, and endangers the health of both mom and baby, but it’s been significantly understudied due to ethical concerns about conducting clinical trials on pregnant women. This has led to a lack of data and information, which doctors now see as more of a danger to pregnant patients rather than participating in a trial.
Lupus is an autoimmune disorder that causes the body’s immune system to attack its own tissues. This leads to inflammation and many symptoms including kidney inflammation, severe fatigue, joint pain and swelling, skin rashes and lesions, chest pain and difficulty breathing, and organ damage. It predominantly affects Black and Hispanic or Latino American women aged 15-45.
Megan Clowse, MD, MPH, chief of the Division of Rheumatology in the Duke Department of Medicine, led the study, which focused on 226 patients with rheumatic diseases who delivered babies at a Duke University hospital since 2013. After a chart review, patients were categorized into groups based on their diagnosis, comparing those with Lupus to those with other rheumatic diseases like Sjogren’s syndrome and rheumatoid arthritis.
Overall, 14% of participants had preeclampsia, including 27% of study participants with Lupus in comparison to 8% of study participants with other rheumatic diseases.
The main finding in this study was that preeclampsia dramatically increased poor infant outcomes. Study results showed that infants born to mothers with preeclampsia were delivered an average of 3 weeks earlier than those without preeclampsia. Those infants were also 4 times as likely to be born preterm, and twice as likely to be admitted to the neonatal intensive care unit. This leads to longer hospital stays and increased medical costs, especially for infants born to mothers with Lupus.
The onset of preeclampsia is sudden and appears after a woman has reached 20 weeks gestational period. “Preeclampsia is scary for people and their spouses. Everybody is terrified because it hits very quickly. One week you're fine. 3 days later, you're not fine and you're at high risk for stroke and seizures,” Clowse said.
The Detrimental Effects of Preterm Birth
“It’s not like they’re born a week or two early, they’re often born earlier than 34 weeks,” Eudy said. “Finding a way to make these pregnancies even 2-3 weeks longer, can really have an impact on the baby and how they develop throughout their childhood,” Eudy continued.
“Preterm birth causes several problems. Some are subtle differences that you might not ascribe in your family to prematurity. But when you look on a population level, you can see higher rates of asthma, cognitive impairment, and developmental delays,” Clowse said.
Preterm birth is a common pregnancy complication. “Even if mom and baby turn out fine clinically, it still sticks with people,” Clowse said. “Some women are left with traumatic experiences related their delivery, which sometimes leads them to not want to get pregnant again,” Clowse said. “They may also always envision their child as sick or vulnerable, even if they’re not particularly ill,” she continued.
Women with preeclampsia also carry a much higher risk of cardiovascular disease. “We don't know if it's that you had this event of preeclampsia and that leads to the development of cardiovascular disease, or if your risk factors for cardiovascular disease set you up for preeclampsia,” Clowse said.
She thinks of pregnancy as a stress test for a person’s cardiovascular ability. “You have to grow a placenta, which is an entirely new highly vascularized organ, fast. You grow that in 9 months, as well as a baby,” Clowse said. “Women who have higher cardiovascular risk factors to start with, don’t build the placenta as well, and it can lead to preeclampsia. Having preeclampsia sets you up for cardiovascular disease, high blood pressure, and other medical conditions later,” she continued.
Closing the Information Gap
The field of reproductive rheumatology is relatively new. “There were only a few rheumatologists in the United States before me who focused on pregnancy,” Clowse said. “There were a few Lupus doctors who also happened to study pregnancy, but their career wasn’t surrounding that. But it wasn’t until the last 5 to 10 years that people found it exciting to study,” Clowse continued. She has been collecting data since 2007 and has added one thousand pregnancies in women with rheumatic diseases to her registries.
Previously, researchers and doctors were very hesitant to conduct clinical trials with pregnant women, but the covid-19 pandemic helped to change that approach. Clowse said trying to figure out whether pregnant women needed to get vaccinated is what really broke the mold.
“It moved people's thinking forward a little bit about the ethical balance of doing trials with pregnant women. Historically, the ethical approach was that it was better not to do clinical trials, because of the dangers it carries. But the pandemic made everyone realize how dangerous it is when we don't have any data about the safety of vaccinations or medications in pregnancy,” Clowse said.
“We've been saying that ‘this [including pregnant patients in clinical trials] is too hard to do, but that has left us without data that we actually need. Patients need data, doctors need data, and right now, we just don't have that,” she continued. Recently however, the National Institutes of Health and U.S. Food and Drug Administration expressed interest in conducting more of these types of trials.
Clowse and Eudy are currently working to close the information gaps and figure out how to lower the chances of developing preeclampsia. “We want to identify preeclampsia earlier to see if someone is on a path to preeclampsia, understand the risk factors for it, and how to prevent it,” Eudy said.
Future Research
Specifically, they are studying whether biomarkers can help predict who will get preeclampsia and whether the recommended aspirin dose should be increased for patients with lupus.
“My number one mission in life is to make sure women with rheumatic diseases can have safe pregnancies,” Clowse said. “What gets us there most successfully is planning the pregnancy, safe medications, and disease control. If you do those things ahead of time, people do a lot better,” she said.