In the JournalsPerspective

New preeclampsia screening method outperforms existing UK guidelines

Preeclampsia screening that utilized biomarkers produced better outcomes than the United Kingdom’s existing National Institute for Health and Care Excellence guidelines, according to findings recently published in Ultrasound in Obstetrics & Gynecology.

Current U.K. guidelines deem women with a history of hypertensive diseases in an earlier pregnancy, or who have autoimmune disease, chronic hypertension, chronic kidney disease, or diabetes mellitus to be at high risk for developing preeclampsia. Women with two or more of the following are also at increased risk for preeclampsia: first pregnancy occurring aged 40 or older, 10 years or more between pregnancies, a BMI higher than 35 kg/m2 and/or a family history of preeclampsia.

“The performance of such an approach, which essentially treats each risk factor as a separate screening test with additive detection rate and screen-positive rate, and the uptake of aspirin by the high-risk group, has not been evaluated by prospective studies,” M.Y. Tan, of King’s College Hospital in London, and colleagues wrote.

In the new screening approach, researchers studied the known risk factors along with a combination of biomarkers: serum pregnancy-associated plasma protein-A data, uterine artery pulsatility indexes, serum placental growth factors, medical histories, maternal characteristics and measurements of mean arterial pressure. A total of 16,747 singleton pregnancies 11 to 13 weeks along in gestation were prospectively analyzed.

Tan and colleagues wrote that utilizing the NICE guidelines yielded a 10.3% detection rate. The new screening approach led to a 30.4% detection rate for all cases of preeclampsia and 40.8% of preterm cases. In addition, researchers found that the preeclampsia detection rate in women of any gestational age whose risk factors were assessed in addition to measurement of mean arterial pressure and serum pregnancy-associated plasma protein-A was 42.5%, which exceeded that of the existing UK method by 12.1% (95% CI, 7.9–16.2%). In screening for preterm preeclampsia that utilized maternal factors, mean arterial pressure and serum placental growth factors, the detection rate was 69%, which surpassed the existing UK method by 28.2% (95% CI, 19.4–37%). When uterine artery pulsatility index was added to this last set of criteria, the detection rate improved to 82.4% which was 41.6% higher than the existing UK method (95% CI, 33.2–49.9%).

“The findings indicate that the use of the simple algorithm based on maternal characteristics and easily measurable markers can identify approximately 80% of women who would go on to develop preterm-[preeclampsia] and would therefore benefit from taking prophylactic aspirin,” according to a press release. “The first-trimester combined test is freely available as a simple and user-friendly risk calculator via http://www.fetalmedicine.org and on the Fetal Medicine Foundation app.”

The U.S. Preventive Services Task Force recommended in 2017 that screening for preeclampsia with BP measurements throughout a patient’s pregnancy take place. – by Janel Miller

Disclosure: Healio Family Medicine was unable to determine the authors relevant financial disclosures prior to publication.

 

Preeclampsia screening that utilized biomarkers produced better outcomes than the United Kingdom’s existing National Institute for Health and Care Excellence guidelines, according to findings recently published in Ultrasound in Obstetrics & Gynecology.

Current U.K. guidelines deem women with a history of hypertensive diseases in an earlier pregnancy, or who have autoimmune disease, chronic hypertension, chronic kidney disease, or diabetes mellitus to be at high risk for developing preeclampsia. Women with two or more of the following are also at increased risk for preeclampsia: first pregnancy occurring aged 40 or older, 10 years or more between pregnancies, a BMI higher than 35 kg/m2 and/or a family history of preeclampsia.

“The performance of such an approach, which essentially treats each risk factor as a separate screening test with additive detection rate and screen-positive rate, and the uptake of aspirin by the high-risk group, has not been evaluated by prospective studies,” M.Y. Tan, of King’s College Hospital in London, and colleagues wrote.

In the new screening approach, researchers studied the known risk factors along with a combination of biomarkers: serum pregnancy-associated plasma protein-A data, uterine artery pulsatility indexes, serum placental growth factors, medical histories, maternal characteristics and measurements of mean arterial pressure. A total of 16,747 singleton pregnancies 11 to 13 weeks along in gestation were prospectively analyzed.

Tan and colleagues wrote that utilizing the NICE guidelines yielded a 10.3% detection rate. The new screening approach led to a 30.4% detection rate for all cases of preeclampsia and 40.8% of preterm cases. In addition, researchers found that the preeclampsia detection rate in women of any gestational age whose risk factors were assessed in addition to measurement of mean arterial pressure and serum pregnancy-associated plasma protein-A was 42.5%, which exceeded that of the existing UK method by 12.1% (95% CI, 7.9–16.2%). In screening for preterm preeclampsia that utilized maternal factors, mean arterial pressure and serum placental growth factors, the detection rate was 69%, which surpassed the existing UK method by 28.2% (95% CI, 19.4–37%). When uterine artery pulsatility index was added to this last set of criteria, the detection rate improved to 82.4% which was 41.6% higher than the existing UK method (95% CI, 33.2–49.9%).

“The findings indicate that the use of the simple algorithm based on maternal characteristics and easily measurable markers can identify approximately 80% of women who would go on to develop preterm-[preeclampsia] and would therefore benefit from taking prophylactic aspirin,” according to a press release. “The first-trimester combined test is freely available as a simple and user-friendly risk calculator via http://www.fetalmedicine.org and on the Fetal Medicine Foundation app.”

The U.S. Preventive Services Task Force recommended in 2017 that screening for preeclampsia with BP measurements throughout a patient’s pregnancy take place. – by Janel Miller

Disclosure: Healio Family Medicine was unable to determine the authors relevant financial disclosures prior to publication.

 

    Perspective
    John Barton

    John R. Barton

    The reported incidence of gestational hypertension and preeclampsia ranges from 10% to 15% of all pregnancies. Poon and colleagues, have reported that a preeclampsia screen in the first trimester combining maternal factors and biomarkers (Fetal Medicine Foundation algorithm) has a better diagnostic accuracy for identifying those at risk for preeclampsia than by maternal characteristics and medical history as suggested by the American College of Obstetricians and Gynecologists (ACOG) and the National Institute for Health and Care Excellence.

    For the 34,573 pregnancies studied by Poon et al, 0.7% developed preeclampsia at 37 or fewer weeks and 1.8% developed preeclampsia at 37 or more weeks. At least one of the ACOG screening criteria was fulfilled in 65.4% of pregnancies and the incidence of preterm preeclampsia was 0.97%. In the subgroup that were Fetal Medicine Foundation screen positive, the incidence of preterm preeclampsia was 4.8% and in those that were Fetal Medicine Foundation screen negative, the incidence was 0.25%. Preterm preeclampsia, however, missed by Fetal Medicine Foundation screen but encompassed in ACOG screening included nulliparity 36/151 (24%), in vitro fertilization therapy 4/12 (25%) and BMI of 30 or greater 30 15/81 (18.5%). Of note, the obesity rate in the Poon and colleagues study was 18% compared to the most recent U.S. data reporting a prepregnancy obesity rate greater than 25%. Further, compared with ACOG screening, 50% of cases of preeclampsia at ≥37 weeks were not detected by the Fetal Medicine Foundation screening.

    Preeclampsia is a complex, multisystem inflammatory syndrome that can originate from multiple causes including impaired trophoblast invasion, placental and endothelial dysfunction, and an imbalance in angiogenic and antiangiogenic factors. ACOG and the National Institute for Health and Care Excellence  guidelines for screening of preeclampsia are a component of routine prenatal care and do not require expensive instrumentation and skill in performing first trimester uterine artery Doppler studies or serum biomarkers. Previous published reports in the U.S. attempting to replicate the diagnostic accuracy of first trimester uterine artery pulsatility index as screening for preeclampsia have not had the same success as the group led by Nicolaides et al in London, England. Further, per the most recent National Vital Statistics Reports for the U.S. from 2016, 22.9% of women began prenatal care after the first trimester and 3.4% of pregnancies represented a twin or triplet gestation; neither therefore eligible for the Fetal Medicine Foundation screening algorithm. In addition, women with chronic hypertension, pregestational diabetes and previous pregnancies with preeclampsia would be managed as high risk regardless of screening and per the U.S. Preventive Services Task Force recommendations would receive low-dose aspirin therapy. There was no formal health economic assessment concerning the implementation of combined screening for preeclampsia in Poon and colleagues report.

    A major concern of screening for preeclampsia without evidence of benefit is the unintended consequences of those identified as at risk, particularly for a test with a very high false positive rate of cases with a very low positive predictive value. Some authors and commercial entities have recommended that those who screen positive should have more frequent visits, more maternal and fetal testing, bed rest, and other interventions that could be potentially harmful to both mother and infant, especially when incorrectly labeled at risk by a test with a high false positive rate.

    References:

    Goetzinger KR, et al. J Ultrasound Med. 2013;doi:10.7863/ultra.32.9.1593.

    Poon LC, et al. Ultrasound Obstet Gynecol. 2018;doi:10.1002/uog.19019.

    Sonek J, et al. Am J Obstet Gynecol. 2018;doi:10.1016/j.ajog.2017.10.024.

    • John R. Barton, MD
    • department of maternal and fetal medicine, Baptist Health Medical Group, Lexington, Kentucky
      Past member, ACOG task force on hypertension in pregnancy

    Disclosures: Barton reports being an investigator for the Preeclampsia Triage by Rapid Assay trial sponsored by Alere.

    Perspective
    Judette Louis

    Judette Louis

    The first reaction I had after reading this study is that it sounded great, that Tan and colleagues’ method could find 82% of cases that would go on to become preeclampsia. This study had the highest prediction value that I have seen.

    Then I read further and saw that a lot of resources were needed to achieve these results and I wondered if it was worth going to the trouble of using all those resources. There are not a lot of things we can do to prevent preeclampsia. We need to consider the practicality of those measures which we are using.

    An analysis of what it would cost to do all the screenings Tan and colleagues mentioned would be helpful to see whether adding all these extra resources would be worth the benefit of determining if a woman is at risk for preeclampsia. Until such a cost-analysis is done, I don’t think primary obstetric providers should change their preeclampsia-related procedures in light of this study.

    • Judette Louis, MD
    • Board of directors, Society of Maternal Fetal Medicine,
      Associate professor, College of Medicine Obstetrics & Gynecology, University of South Florida,
      Medical director of maternal-fetal medicine at Tampa General Hospital