During a scheduled obstetrics clinic visit early last year, Hannah Papazoglou got some unwelcome news. While she completed an ultrasound exam, Papazoglou, who was 21 weeks pregnant, learned that her providers had diagnosed her with high blood pressure. She’d also been diagnosed with high blood pressure at 16 weeks.
It wasn’t the first time Papazoglou, 32, had encountered the problem. She’d also had high blood pressure, known as gestational hypertension, late in the pregnancy of her first child. Her blood pressure had returned to normal after that birth. She’d also regularly gotten normal readings when she’d taken her blood pressure at home during the second pregnancy. It only seemed to rise when she came to the clinic.
“I was concerned, but I thought it might be ‘white coat hypertension,’” said Papazoglou – the kind induced by anxiety in the company of doctors and other health care providers.
After the ultrasound, Papazoglou and her husband, Adam, had another question to mull. Her clinic providers asked if she’d be willing to enroll in a national trial – called the CHAP (Chronic Hypertension and Pregnancy) Project – aimed at determining the potential benefit or harm of administering blood pressure-lowering medications to pregnant women with mild-to-moderate hypertension (above 140/90 but lower than 160/105). Women who enroll in the project are randomized to either receive blood pressure medication to maintain blood pressures below 140/90 or to the “no treatment” arm of the study where patients only receive medication if their pressures rise above 160/105.
It wasn’t an easy decision. Aside from her experience with finicky blood pressure readings and return to normalcy after her first pregnancy, Papazoglou worried about taking any medications that might affect her unborn child.
“I thought, ‘What if I am put on the medication and something happens with my baby?’” Papazoglou said. “I was worried that my blood pressure might go too low. But I also knew that low birth weight can be a problem with people who have high blood pressure. I was aware of the risks.”
Papazoglou ultimately decided to enroll in the trial – she was the first at UCHealth University of Colorado Hospital on the Anschutz Medical Campus. Papazoglou was prepared to take the medication, but she was randomized to the “no treatment” arm of the study. Her second son arrived healthy on March 2, 2018, and Papazoglou’s blood pressure settled back to normal about a month later.
Her experience and ambivalence illustrate the importance of the CHAP Project, said Dr. Emily Su, a maternal-fetal medicine specialist who is the University of Colorado principal investigator for the multi-center clinical trial.
There is ample evidence of the “catastrophic” risks caused by high blood pressure during pregnancy, Su said. They include stroke and separation of the placenta from the uterine wall, which can lead to premature birth. But professional organizations like the American College of Obstetricians and Gynecologists and American Society of Hypertension do not recommend prescribing blood pressure medications for women with mild-to-moderate hypertension, worrying that the treatment could dangerously reduce blood flow to the uterus and placenta.
The uncertainty is precisely why the CHAP Project is important, Su said.
“As a clinician, I think this trial is incredibly important because it asks a fundamental, age-old question to which we still don’t have the answer,” she said. “We know that treating moms with severely elevated blood pressure decreases risks to maternal health, but we have no idea how treating mild-to-moderate range blood pressures affects maternal and fetal outcomes. There could be significant benefit, or alternatively, there could be other downstream consequences of decreasing maternal blood pressure in a woman who only has mild-to-moderate hypertension. We just don’t know.”
The CHAP project also highlights another significant problem in medicine: relatively little is known about the overall effects of medications on pregnancy because pregnant women have been largely excluded from participating in clinical trials. It was only recently that the Department of Health and Human Services (DHHS) removed pregnant women from a list of groups deemed “vulnerable to coercion or undue influence” in making decisions about participating in research studies.
In addition, an April 2018 draft document from DHHS, the FDA and the Center for Biologics Evaluation and Research noted that while some pregnant women require medications to treat chronic and acute medical problems, there is little clinical data available to inform the women and their providers about the risks. “The frequent lack of information based on clinical data often leaves the health care provider (HCP) and the patient reluctant to treat the underlying condition, which in some cases may result in more harm to the woman and the fetus than if she had been treated,” the authors concluded.
As Su put it, “So much of obstetrics is rooted in tradition because there haven’t been a ton of trials and interventions.” Addressing the CHAP Project, she added, “If we end up finding out that there is a benefit in pregnancy [of treating mild-to-moderate high blood pressure], this could also lead to more clinical research trials that investigate other questions surrounding maternal health and pregnancy outcome.”
Enrollment challenges and support
Meanwhile, recruiting patients for the trial has been a relatively slow process, said Jocelyn Phipers, nurse coordinator for the Obstetrics Research Team at the University of Colorado School of Medicine. Phipers is among five nurses who work with the UCHealth obstetricians and midwives to find eligible patients. Women must be enrolled before their 23rd week of pregnancy and must have two separate high blood pressure readings on the same day in order to be randomized.
“The team has spoken with many interested participants; however, due to normal blood pressure decreases in the second trimester of pregnancy, most patients do not have the required elevated blood pressures until after their 23rdweek, which excludes them from the study,” Phipers said.
She added that women who are already on medication may have reservations about potentially being in the “no treatment” arm and having to discontinue medication for the trial.
“The study team encourages these patients to speak with their providers about the risks and benefits of continuing medication in their pregnancy before deciding whether to participate,” Phipers said.
For patients who meet the criteria, the team works with their providers to ensure it is appropriate to approach the women and explain the trial. The Obstetrics Research Team facilitates consent and enrollment and meets with the patients at every clinic visit to monitor their blood pressure. They also work with providers to adjust medications for patients in the treatment arm to maintain blood pressures below 140/90. Patients can also consent to an optional collection of umbilical cord blood and maternal blood at delivery. The team ships the samples to the University of Alabama-Birmingham, the main study site.
The nurse team is available around the clock to answer questions from patients, Phipers added. “I think they feel as though they have an extra set of eyes on them,” she said. “They have a nurse to check in with them and see how they’re feeling and how the pregnancy is going.” Six weeks after they deliver, patients also attend a follow-up visit.
Growing the body of knowledge
While Hannah Papazoglou didn’t get blood pressure medication during her pregnancy, she feels her participation in the trial could help to increase understanding of conditions like preeclampsia – dangerously high blood pressure during pregnancy.
“I think that any information that is made known would be beneficial for future generations,” she said.
For her part, Su believes that “current dogma” suggests that short periods of mildly elevated blood pressure like Papazoglou experienced during her pregnancies probably aren’t a long-term health risk to the patient herself. But she added a caveat that is at the heart of the CHAP Project investigation.
“At the end of the day, it highlights just how much is unknown about human pregnancy,” she said.
For more information about the CHAP Project, contact Jocelyn Phipers: firstname.lastname@example.org.