Karen Titus
July 2026—Among its many peculiarities, medicine dwells in interstitial spaces—between seeing a problem and addressing it; between the (in)actions of one specialty and another; between practice and practice guidelines; between overtreatment and targeted treatment; between widespread access and boutique care.
Within each space lie the particulars, where a pivot becomes pivotal. Between pregnancy and delivery, and maternal health and fetal health, lies screening for preeclampsia.
It’s also been a matter of much frustration.
“Of all the conditions we screen for” in pregnant patients, says Dr. Hallahan, “preeclampsia is the only one we can actually prevent. So it makes absolutely no sense not to screen for this. It’s one of the top three causes of maternal mortality in the United States. It’s an area where we are lagging the rest of the world.”
It’s time, he says, to make first-trimester preterm preeclampsia screening the standard of care, using an algorithm developed by the London-based Fetal Medicine Foundation to identify at-risk patients. It uses two maternal serum biomarkers—pregnancy-associated plasma protein A and placental growth factor—along with uterine artery pulsatility index and mean arterial pressure.
This is not a revolutionary idea, says Dr. Hallahan, who spoke on the topic in an interview with CAP TODAY and in a Compass Group presentation this spring. The better mousetrap has been built, and much of the world has already beaten a path to its door. “Most of the major professional societies have some sort of statement regarding the use of biomarkers for screening for preeclampsia,” he says, pointing to the Society of Obstetricians and Gynecologists of Canada, Royal College of Obstetricians and Gynecologists, and Royal Australian and New Zealand College of Obstetricians and Gynecologists, as well as the International Federation of Gynecology and Obstetrics and the International Society of Ultrasound in Obstetrics and Gynecology.
Currently, however, the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine do not, he says.
In Dr. Hallahan’s experience, this is part of a familiar pattern. “When we first started doing first-trimester Down syndrome screening, which eventually became standard of care, they were at least 10 years behind relative to the rest of the world. And that’s kind of where we’re at now.”
That “now” is an especially worrisome time, Dr. Hallahan says, given that the incidence of preeclampsia has risen 25 percent in the past 20 years. Though the reasons for this aren’t fully clear, he says, “Certainly things such as obesity rates don’t help.”
This comes on top of already difficult numbers.
Dr. Hallahan notes that preeclampsia affects five to eight percent of all pregnancies. In the United States, 16 percent of all maternal deaths are due to preeclampsia; moreover, it results in 10,500 baby deaths annually. He also points to one large study of pregnancy-related mortality in California, which found that 60 percent of preeclampsia deaths are preventable (Main EK, et al. Obstet Gynecol. 2015;125[4]:938–947).
“Even early onset, which affects 0.5 percent of the population, far outstrips every other condition that we screen for prenatally combined, including Down syndrome, trisomy 18, trisomy 13, open neural tube defects, Smith-Lemli-Opitz syndrome, microdeletions, et cetera,” he says. “They don’t compare to the preeclampsia numbers.”
It’s the only condition, he adds, that endangers the life of both patients. The complications can be severe for parent (seizures, stroke, organ damage, future cardiovascular disease, death) and fetus (growth restriction, placental abruption, preterm birth and related concerns, hypertension/cardiovascular disease later in life, stillbirth).
The key to reversing this is to intervene earlier, he says. Preeclampsia is a multisystem progressive disorder; after 20 weeks gestation, it’s characterized as new-onset hypertension and proteinuria, or hypertension and end-organ dysfunction, with or without proteinuria. Symptoms include intrauterine growth restriction, proteinuria, low platelets, headaches, vision disturbances, and nausea. But by the time symptoms emerge, “it’s because end-organ dysfunction has already started, so it’s too late.”
“Timing in preeclampsia is so important,” he says. The 11- to 14-week window for first-trimester screening is small—more casement than French door. “If you miss it, you’ve lost the opportunity.” Ditto for starting aspirin. If it’s not started before 16 weeks, “you’ve lost the opportunity to prevent it.” And when it develops later, “it comes on like a freight train,” he says.
PAPP-A has been used as a first-trimester Down syndrome marker since the mid-1990s. Physicians have also long known that low levels of PAPP-A were associated with preeclampsia, Dr. Hallahan says. “But we didn’t have other markers to combine it with.” In the past, he and his laboratory colleagues would indicate in the Down syndrome report if the PAPP-A result was extremely low, with a footnote explaining that values below a specific level were associated with increased risk of preeclampsia.
The discovery of placental growth factor (PlGF) made a combination screen a viable option. The ASPRE trial (Rolnik DL, et al. N Engl J Med. 2017;377[7]:613–622) was a turning point for demonstrating the value of the Fetal Medicine Foundation’s algorithm. “That’s really where it was proven,” says Dr. Hallahan. “Since then, worldwide, it’s been validated in almost a dozen different countries.”
Enlisting the support of clinical colleagues can be tricky, he notes.
The scope and seriousness of the problem draw his colleagues’ attention, he says, “but it’s difficult not having the ACOG recommendation yet.” How do laboratories step into a situation to improve practice without stepping onto someone else’s professional territory? “It’s a matter of education,” he says, “getting out and talking to the physicians and presenting the data from [the] ASPRE trial.” In short, it means convincing them that preeclampsia can be managed much more proactively.
At Northwell, Dr. Hallahan says he works closely with the maternal-fetal medicine department, given that the screening test includes not only the laboratory markers but also uterine artery Doppler and mean arterial pressure. “So we have to have very good collaboration with clinicians,” he says, to obtain and coordinate the information needed to provide the risk value.
One especially effective approach, Dr. Hallahan has found, is to show colleagues the actual performance of the current ACOG/Society for Maternal-Fetal Medicine guidelines.
How do those conversations unfold?
“Well, you will have clinicians who will talk about aspirin a lot,” he says.
ACOG and SMFM suggest a protocol involving low-dose (81 mg/day) aspirin prophylaxis for patients who are at increased risk for preeclampsia; indeed, it’s recommended by nearly all professional societies worldwide. But, as Dr. Hallahan notes, screening in the United States is different from that in many other Western countries.
In this country, broad reliance on aspirin may be simple and inexpensive, but it also borders on pointless. The guidelines rely on counting risks from lists of high- and moderate-risk factors to determine who should receive aspirin. But the list is so generalized and extensive, he says, that more than half the population will be considered at increased risk. Some five percent of patients will have at least one high-risk factor, and 45.5 percent will have two or more moderate-risk factors; both scenarios would qualify the patient for aspirin therapy. And new U.S. Preventive Services Task Force recommendations call for patients with just one moderate-risk factor to consider low-dose aspirin, which increases the targeted population of low-dose aspirin-eligible patients to 80 to 85 percent.
Says Dr. Hallahan, “It’s not even screening anymore.” He minces no words about the current approach. “The recommendation is to screen, and then treat with aspirin. The problem is, you have a lousy screening tool with what ACOG and SMFM provide. All we’re saying is, ‘We have a better way.’”
“If everybody is at increased risk, basically nobody is at increased risk,” he says. The screening tool is not only bad, he adds, but also used inconsistently by clinicians.
Yet aspirin continues to steer the conversations. “The common argument that you run into is, ‘Why not just give aspirin to everybody?’”
Dr. Hallahan says that when clinicians talk about using low-dose aspirin, many are drawing a false equivalency to folic acid. When researchers discovered the latter’s role in preventing open neural tube defects, the amount was increased in the prenatal vitamin; it was also added to breads and cereals.
But, Dr. Hallahan says, “Aspirin is not a vitamin; it is a drug you are prescribing during pregnancy. I don’t think anyone would recommend putting aspirin into breads and cereals.” And while aspirin is generally considered quite safe during pregnancy, “There will be very low-incidence side effects.”
Giving aspirin to everybody should not be the default answer, he continues. “To me, we’re much better off taking a more intelligent and focused approach. This way we can focus on the problem, and not just pan-give out aspirin to everybody.”
The other reason to rein in aspirin use “is that it’s only effective if the patient takes it religiously,” he says, adding that studies have shown that the adherence rate needs to be at least 90 percent.
But even the prenatal vitamin doesn’t reach 90 percent, he says. Likewise, simply saying across the board that every pregnant person is at risk of preeclampsia and should take aspirin is unlikely to be effective. Screening, on the other hand, provides patients with their specific risk, and it lets physicians identify and focus on a small subset of those who are at increased risk.
This would include educating patients about the signs/symptoms of preeclampsia. Studies have shown that the biggest reason most cases are considered preventable is that signs/symptoms can go unrecognized by patients and even providers, says Dr. Hallahan. “They simply don’t get help in time.”
But because the screening is done early, “You can also prescribe low-dose aspirin before 16 weeks—which is necessary—and can monitor that patient’s aspirin adherence,” he says. “Or at least educate them about how important adherence is.”
The biomarkers of preeclampsia are directly or indirectly related to the transformation of the spiral arteries. “In the pathophysiology of preterm preeclampsia,” he says, “it is caused by a failure of that transformation.”
These arteries are corkscrew-shaped vessels that traverse the endo- and myometrium, he says. In nonpregnant patients, they remain tightly coiled, very narrow vessels that allow for very little blood flow. When a patient becomes pregnant, trophoblast cells invade the spiral arteries, which become large, funnel-shaped vessels that allow for high blood flow and good perfusion of the placenta, he says. With preeclampsia, the transformation doesn’t occur or “doesn’t go far enough.”
PAPP-A is a key regulator of insulin-like growth factor bioavailability, which is a known proangiogenic factor. PlGF is also a proangiogenic factor, produced predominantly by the placenta. And soluble fms-like tyrosine kinase 1, sFlt-1, is an antiangiogenic factor that mediates PlGF and vascular endothelial growth factor. Uterine artery Doppler is a surrogate for measuring perfusion of the placenta. And mean arterial pressure looks at systemic resistance—the higher the resistance, the higher the risk for preeclampsia.
Using the multimarker screening algorithm is transformational, Dr. Hallahan says. “We can detect 80 percent of preterm preeclampsia,” that is, deliveries that will occur prior to 37 weeks due to preeclampsia. “And remember, we’re doing this at 10 to 14 weeks, so we have a lot of lead time with this test.”
“We do even better with the more severe cases,” he continues. If it’s early-onset preeclampsia—before 34 weeks—90 percent of cases will be detected. That rises to more than 90 percent at less than 32 weeks. “This significantly increases our sensitivity and specificity relative to the ACOG/SMFM checklist method. We can shift management of preeclampsia from being reactionary in the second trimester, when the patient comes crashing through the emergency room doors, to a prediction and prevention model.”
Fine-tuning the screening—or rather, actually screening—also reduces patient anxiety and allows for much better allocation of resources, Dr. Hallahan says.
For those who are truly at risk, there is ample time to educate patients. It also allows for targeted surveillance, including intensified maternal and fetal monitoring.
And, of course, intervening with low-dose aspirin. “As long as you start it prior to 16 weeks,” he says—right before the second wave of trophoblast invasion of the spiral arteries—“it can prevent 60 to 90 percent of preterm and early-onset preeclampsia cases.” Timing is critical. Aspirin started after 16 weeks brings less than a 20 percent reduction in incidence. Further, aspirin will not help with term preeclampsia, which “probably has a completely different etiology than the early-onset form of the disease.”
Prediction and prevention are a powerful duo. But prognosis is critical as well.
In the second and third trimesters, he says, “we have the tools for the prognosis of preeclampsia.” There are currently two FDA-approved tests for sFlt-1/PlGF ratio on the market (Thermo Fisher Scientific and Roche).
The approvals were based on data from the PRAECIS study (Thadhani R, et al. NEJM Evid. 2022;1[12]:EVIDoa2200161), says Dr. Hallahan, in which the sFlt-1/PlGF ratio was measured in patients hospitalized with hypertensive disorders of pregnancy. The ratio was high in cases that developed severe preeclampsia within two weeks but low in cases that did not progress to severe preeclampsia. The ratio level cutoff was 40. Sensitivity was 93.5 percent; specificity was 74.9 percent. The positive predictive value, he says, was fairly high: 65.2 percent. “But like most screening tests, the real power is in the negative predictive value”—in this case, 95.8 percent.
“So how does this help us clinically?” Dr. Hallahan asks. When taken in total clinical context, it allows physicians to increase surveillance management and make better decisions about whether to discharge or admit a patient, or make a referral to another institution. It can also help refine the timing of corticosteroids, which need to be administered between seven days and 24 hours before a C-section. “If you don’t know when the patient is going to progress to severe preeclampsia, which will force delivery, you don’t know when to start the corticosteroids. This gives some insight to that timing, signaling when to prepare for an early delivery.”
If Dr. Hallahan’s passion for this topic is not yet evident, he offers another stark observation.
“Preeclampsia is a preventable, treatable pregnancy complication that still devastates families today,” he says. “And your chances of survival are largely dictated by your race and income status.”
While aspirin is not appropriate for everyone, he says, screening is.
Dr. Hallahan focuses on lack of access to care as well as implicit bias and systemic racism as having particular impact on preeclampsia. The first translates to delayed or infrequent prenatal visits and thus lost opportunities to screen. And the second has been shown to affect diagnosis, treatment, and provider-patient trust and communication.
“Black women start out already behind the eight ball because they have a significantly higher background risk for incidence, severity, and mortality rates,” he says. “You add on top of that implicit bias and systemic racism, which leads to these delays. Black women are more likely to experience a dismissal of symptoms. They’re more likely to have delayed treatments. And they’re more likely to get bad information or not enough information and lack informed consent. These things conspire against Black women and their outcomes in preeclampsia.”
Patients who are socioeconomically challenged and lack access to quality care “have a terrible situation.” Lack of insurance, geographic and transportation barriers, child-care challenges, and difficulties getting time off work “all lead to the dreaded delays.”
Dr. Hallahan and his Northwell colleagues implemented the screen about a year ago. “It’s gone relatively smoothly,” he says of the centers where it’s now in place. The goal is to have other sites adopt it as well. “We’re starting to make very good traction, and we’re starting to put in the work of training the sonographers on doing the uterine artery Dopplers.”
It’s critical to make the screening available at all sites, he says, noting the very real disparities across various patient populations. “We make sure that clinicians are aware that preeclampsia disproportionately affects the Black population.”
Northwell’s Center for Maternal Health is focused on addressing disparities. But it’s a challenge, and Dr. Hallahan worries that overall adoption will remain limited. “We can actually widen the disparities if the screening only stays in boutique settings,” used primarily by patients who can afford to pay out-of-pocket or who have superior health insurance. “We don’t want this to be a boutique test.”
Action without equity will never suffice, in other words. His focus is clear: to get every Northwell Ob-gyn and maternal-fetal medicine specialist to do the testing “so it is available to all.”
He adds: “New screening tools offer significant hope for earlier and more accurate prediction, prevention, and prognosis, but the full potential will be realized only if they are applied equitably. Achieving better maternal and fetal health outcomes for all requires both innovation in screening and commitment to health equity.”
Karen Titus is CAP TODAY contributing editor and co-managing editor.