ASPRE Trial: Incidence of Preterm Preeclampsia in Patients Fulfilling ACOG and NICE Criteria According to Risk by FMF Algorithm

The current approach to screening for preeclampsia (PE) is to identify risk factors from maternal demographic characteristics and medical history (maternal factors). According to the National Institute for Health and Care Excellence (NICE), in the United Kingdom, women are considered to be at high risk of developing PE if they have any one high-risk factor (hypertensive disease in previous pregnancy, chronic hypertension, chronic renal disease, diabetes mellitus, or autoimmune disease) or any 2 moderate-risk factors (nulliparity, age ≥40 years, body mass index [BMI] ≥35 kg/m², family history of PE, or interpregnancy interval >10 years). In the United States, according to the American College of Obstetricians and Gynecologists (ACOG), women are considered to be at high risk of developing PE if they have any of the following: PE in previous pregnancy, chronic hypertension, chronic renal disease, diabetes mellitus, systemic lupus erythematosus or thrombophilia, nulliparity, age older than 40 years, BMI of 30 kg/m² or greater, family history of PE, or conception by in vitro fertilization. Consequently, the approach recommended by NICE and ACOG essentially treats each risk factor as a separate screening test with additive detection rate and screen-positive rate. An alternative approach to screening, developed by the Fetal Medicine Foundation (FMF), allows estimation of individual patient-specific risks of PE requiring delivery before a specified gestational age. According to these authors, the performance of screening for preterm PE by the FMF algorithm is superior to the methods recommended by NICE and ACOG, and the best method of selecting patients that would benefit from prophylactic use of aspirin is the method recommended by the FMF. However, obstetricians may be reluctant to withhold treatment from women who are screen positive by the NICE or ACOG methods but screen negative by the FMF method. The researchers conducted a secondary analysis of a prospective, multicenter study in singleton pregnancies at 11 + 0 to 13 + 6 weeks' gestation in women booking for routine pregnancy care at 13 maternity hospitals. The study population consisted of women recruited to the ASPRE study. Eligibility criteria for the trial were maternal age 18 years or older, no serious mental illness or learning difficulty, and singleton pregnancy with live fetus without major abnormality demonstrated on the 11- to 13-week scan. In this study, the authors included pregnancies delivered at greater than or equal to 24 weeks' gestation. During the screening study, 8775 women were evaluated, and 59 subsequently developed preterm PE. During the second phase, 25,798 women were screened and 159 developed preterm PE. The FMF test is the previously reported algorithm for first-trimester assessment of risk for PE by maternal factors, MAP, UtA-PI, PAPP-A, and PlGF. The study population consisted of 34,573 pregnancies that were screened during the first or second phase of the ASPRE study, of which an estimated 239 (0.7%) cases developed preterm PE and 630 (1.8%) term PE. At least one of the ACOG criteria was fulfilled in 22,287 (64.5%) pregnancies, and the incidence of preterm PE was 0.97%(95% CI, 0.85%-1.11%); in the subgroup that was screen-positive by the FMF algorithm, the incidence of preterm PE was 4.80% (95% CI, 4.14%-5.55%), and in those that were screen-negative, it was 0.25% (95% CI, 0.18%-0.33%), with a relative incidence in FMF screen negative to FMF screen positive of 0.051 (95% CI, 0.037-0.071). In 1392 pregnancies (4.0%), at least one of the NICE high-risk criteria was fulfilled, and in this group, the incidence of preterm PE was 5.17% (95% CI, 4.13%-6.46%); in the subgroups of screen positive and screen negative by the FMF algorithm, the incidence of preterm PE was 8.71% (95% CI, 6.93%-10.89%) and 0.65% (95% CI, 0.25%-1.67%), respectively, and the relative incidence was 0.075 (95% CI, 0.028-0.205). In 2360 pregnancies (6.8%) fulfilling at least 2 of the NICE moderate-risk criteria, the incidence of preterm PE was 1.74% (95% CI, 1.28%-2.35%); in the subgroups of screen positive and screen negative by the FMF algorithm, the incidence was 4.91% (95% CI, 3.54%-6.79%) and 0.42% (95% CI, 0.20%-0.86%), respectively, and the relative incidence was 0.085 (95% CI, 0.038-0.192). The authors concluded that the FMF risk-based screening method is preferable to the strategy recommended by ACOG or NICE.