The following is a summary of “Accuracy of placental growth factor alone or in combination with soluble fms-like tyrosine kinase-1 or maternal factors in detecting preeclampsia in asymptomatic women in the second and third trimesters: a systematic review and meta-analysis,” published in the SEPTEMBER 2023 issue of Obstertrics and gynecology by Chaemsaithong, et al.
For a study, researchers sought to comprehensively assess the diagnostic accuracy of maternal circulating placental growth factor (PlGF) alone or in combination with soluble fms-like tyrosine kinase-1 (sFlt-1), as well as PlGF-based models (combining PlGF with maternal factors or other biomarkers) during the second or third trimester for predicting the subsequent development of preeclampsia in asymptomatic women.
A systematic review was conducted using various databases from January 1, 1985, to April 15, 2021, including MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. The study focused on asymptomatic pregnant women with singleton pregnancies who were beyond 18 weeks’ gestation and had a risk of developing preeclampsia. Only cohort or cross-sectional test accuracy studies were included, which reported preeclampsia outcomes, provided tabulation of 2×2 tables, had follow-up data available for more than 85% of participants, and evaluated the performance of PlGF alone, sFlt-1/PlGF ratio, or PlGF-based models.
Given the substantial heterogeneity among the included studies, hierarchical summary receiver-operating characteristic (HSROC) curves were generated. Various statistical measures, such as diagnostic odds ratios and other relevant parameters, were computed to compare the performance of different diagnostic methods. The quality of the studies was assessed using the QUADAS-2 tool.
The search identified 2,028 citations, of which they carefully assessed 474 studies by examining their full texts. Ultimately, 100 published studies were found to meet the eligibility criteria for qualitative evaluation, while 32 met the quantitative synthesis criteria. Among these, 23 studies focused on assessing the performance of placental growth factor (PlGF) testing for predicting preeclampsia during the second trimester. Within these 23 studies, 16 of them (accounting for 27 entries) reported on the performance of the PlGF test on its own, 9 studies (with 19 entries) reported on the soluble fms-like tyrosine kinase-1–placental growth factor (sFlt-1/PlGF) ratio, and 6 studies (comprising 16 entries) reported on PlGF-based models. Similarly, 14 studies delved into the performance of PlGF testing for preeclampsia prediction in the third trimester.
Among these, 10 studies (with 18 entries) reported on the PlGF test as a standalone predictor, 8 studies (with 12 entries) focused on the sFlt-1/PlGF ratio, and 7 studies (with 12 entries) explored PlGF-based models. Regarding the second trimester, PlGF-based models exhibited the highest diagnostic odds ratio for predicting early-onset preeclampsia in the overall population, surpassing the diagnostic performance of PlGF alone and the sFlt-1/PlGF ratio. Specifically, PlGF-based models achieved a diagnostic odds ratio of 63.20 (with a 95% CI ranging from 37.62 to 106.16). In contrast, the sFlt-1/PlGF ratio had a diagnostic odds ratio of 6.96 (with a 95% CI between 1.76 and 27.61), and PlGF alone had a diagnostic odds ratio of 5.62 (with a 95% CI between 3.04 and 10.38). Furthermore, in the unselected population, PlGF-based models also outperformed PlGF alone in predicting any-onset preeclampsia, with a diagnostic odds ratio of 28.45 (95% CI, 13.52–59.85), whereas PlGF alone had a diagnostic odds ratio of 7.09 (95% CI, 3.74–13.41).
In the third trimester, PlGF-based models exhibited better predictive performance for any-onset preeclampsia than PlGF alone. However, their predictive performance was similar to that of the sFlt-1/PlGF ratio. Specifically, PlGF-based models achieved a diagnostic odds ratio of 27.12 (95% CI, 21.67–33.94), while PlGF alone had a diagnostic odds ratio of 10.31 (95% CI, 7.41–14.35), and the sFlt-1/PlGF ratio had a diagnostic odds ratio of 14.94 (95% CI, 9.42–23.70).
In the second trimester, the combination of placental growth factor (PlGF) with maternal factors and possibly other biomarkers showed the highest predictive performance for early-onset preeclampsia in the entire population. However, during the third trimester, PlGF-based models exhibited better predictive capabilities for any-onset preeclampsia compared to PlGF alone, although their performance was similar to that of the soluble fms-like tyrosine kinase-1–placental growth factor (sFlt-1/PlGF) ratio.
This comprehensive meta-analysis revealed a substantial number of diverse studies. Therefore, there is a pressing need for the development of standardized research methodologies utilizing consistent models that incorporate serum PlGF, maternal factors, and potentially other biomarkers. This standardization is crucial for accurately predicting preeclampsia. Identifying individuals at risk through these standardized approaches could prove highly beneficial for enabling intensive monitoring and optimizing the delivery timing in pregnant individuals.