Third-Trimester Preeclampsia Screening Still Worthwhile, Data Suggest

It’s worth screening women for preeclampsia risk in the third trimester when they’re 35 to 36 weeks pregnant, not just earlier in the pregnancy, to assess who might still be vulnerable to developing the condition thereafter, a new observational analysis suggests.

Such patients might benefit from timed birth at 37 weeks to avoid preeclampsia, Laura A. Magee, MD (Addison House, Guy’s Campus, London, England), note in their paper published yesterday in Hypertension. However, they say, this strategy of inducing labor requires further study in a randomized controlled trial.

“Term preeclampsia,” occurring at 37 weeks and beyond, has unique aspects that set it apart from “preterm preeclampsia” that occurs beforehand, Magee explained to TCTMD.

“Preterm preeclampsia is sort of the ‘poster child’ that attracts the attention, because tiny babies and incubators and things, they're really emotive,” she observed. “But about 75% of preeclampsia occurs at term gestational age, and importantly, the majority of the complications for moms and a substantial proportion of the complications for babies actually occur at term because of the sheer numbers of women and babies affected.”

And while low-dose aspirin during pregnancy can reduce the risk of preterm cases, there’s no known way to prevent term preeclampsia, Magee stressed. Even so, screening not just early but closer to delivery is a worthy pursuit, she added.

“No matter how accurate the mechanism is that you use in early pregnancy to identify women at increased risk, it doesn't accurately predict term disease,” said Magee. “Like most prediction, you get better and better at it the closer you are to the event. . . . So you need to look at it at 35 to 36 weeks. Our perspective is that this is worth considering, because the majority of the preeclampsia is yet to come.”

For pregnant women, the results of screening can help them and their partners to both mentally prepare and make informed decisions about what steps, if any, to take, she added.

There also are implications for a woman’s health over her lifetime, as it’s been well established that preeclampsia and gestational hypertension translate into higher CV risk many decades later.

“What we don't know is whether, if we prevent preeclampsia, we will decrease that cardiovascular risk. [It’s unknown] how much is driven by underlying risk factors and how much may be direct damage related to the preeclampsia. There's far more evidence for the former than the latter, but it remains a theoretical possibility that prevention of that preeclampsia may be beneficial in and of itself,” Magee commented.

Screening Tools and Timing of Birth

For their study, Magee and colleagues retrospectively analyzed data from two cohorts of pregnant women who gave birth to babies without major anomalies ≥ 24 weeks’ gestation at two UK-based maternity hospitals. They used information gathered during routine visits to gauge preeclampsia risk with several screening tools: UK National Institute for Health and Care Excellence (NICE) guidance and the Fetal Medicine Foundation (FMF) competing-risks model, as well as a model based on the latter that further stratified women into five risk categories.

The NICE guidance considers clinical factors like comorbidities, older age, family history, and higher body mass index, among other things. The FMF model also includes medical history and demographic information with the addition of metrics like mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor (PIGF) or, alternatively, serum concentration of pregnancy-associated plasma protein-A (PAPP-A).

What we don't know is whether, if we prevent preeclampsia, we will decrease that cardiovascular risk. Laura A. Magee

At 11-13 weeks’ gestation, 57,131 women were screened using these tools and among them 1,138 (2%) developed preeclampsia at 37 weeks or later. During routine visits at 35-36 week’s gestation, 29,035 women were screened and 619 (2.1%) developed preeclampsia at 37 weeks or later.

Pregnancy outcomes were similar between these two groups, as were most patient characteristics. Women delivered at 40 weeks on average, about two-thirds had spontaneous onset of labor, and one-quarter gave birth via cesarean section.

Although the various screening tools performed slightly differently, researchers found that using them at 35-36 weeks, as opposed to at 11-13 weeks, prevented a greater proportion of term preeclampsia. The later screening time also had the lowest number of induced deliveries required to prevent one case of term preeclampsia.

Use of the FMF competing-risks model at 35-36 weeks was better at identifying women who could benefit from timed birth at 37 weeks than the NICE guidance, with the intervention reducing preeclampsia cases by 59.8% (vs 28.8%) and having a lower the number-needed-to-deliver (6.9 vs 16.4). Applying risk stratification to that model allowed similar preeclampsia prevention (57.2%) and a similar number-needed-to-deliver (8.4), and in the process required fewer women to have timed birth at 37 weeks. NICE guidance based on clinical factors alone was a less-effective screening tool.

Magee said that some clinicians are already screening their pregnant patients at 35-36 weeks, though it’s an uncommon practice.

But exactly what’s to be done with that information gleaned from screening hasn’t yet been established, she noted. “These are observational data. They are suggestive that this is a strategy that may be highly effective, particularly [when] risk is personalized. So, women who are at very high risk, like at least a 50% risk of developing preeclampsia at term, are recommended for timed initiation of birth at 37 weeks,” especially since they have a higher risk of going into spontaneous labor ahead of the expected delivery date.

Others might be better suited to timed birth at 38 weeks based on their risk level—the idea is to target those most likely to benefit while minimizing the potential for harm, Magee continued. “Of course the risk of developing preeclampsia at term is rising as gestation goes on. And the risk of newborn health problems from being born closer to 37 weeks as opposed to farther away is going down just based on maturity. So any timed birth is a balance of those two things.”

Importantly, “timed birth by labor induction is an intervention that can be offered around the world. You don't need expensive medications: labor can be induced by a mechanical means with [for example] a Foley catheter, and it's highly effective,” she emphasized.

Thus, the researchers point out, the strategy might be particularly useful in regions where the capacity to care for women with preeclampsia is limited. These under-resourced settings are “where the vast majority of women with preeclampsia die, and where timed birth can be offered easily and inexpensively,” they observe. Even in high-income countries, there are rural areas where access to care could be a challenge, Magee noted to TCTMD.

As for next steps, the Fetal Medicine Foundation is funding a trial that’s soon set to begin and will look at the best timing of birth to prevent preeclampsia, she said.