Toward a new taxonomy of obstetrical disease: improved performance of maternal blood biomarkers for the great obstetrical syndromes when classified according to placental pathology
Issued Date
2022-10-01
Resource Type
ISSN
00029378
eISSN
10976868
Scopus ID
2-s2.0-85139536198
Pubmed ID
36180175
Journal Title
American Journal of Obstetrics and Gynecology
Volume
227
Issue
4
Start Page
615.e1
End Page
615.e25
Rights Holder(s)
SCOPUS
Bibliographic Citation
American Journal of Obstetrics and Gynecology Vol.227 No.4 (2022) , 615.e1-615.e25
Suggested Citation
Romero R., Jung E., Chaiworapongsa T., Erez O., Gudicha D.W., Kim Y.M., Kim J.S., Kim B., Kusanovic J.P., Gotsch F., Taran A.B., Yoon B.H., Hassan S.S., Hsu C.D., Chaemsaithong P., Gomez-Lopez N., Yeo L., Kim C.J., Tarca A.L. Toward a new taxonomy of obstetrical disease: improved performance of maternal blood biomarkers for the great obstetrical syndromes when classified according to placental pathology. American Journal of Obstetrics and Gynecology Vol.227 No.4 (2022) , 615.e1-615.e25. 615.e25. doi:10.1016/j.ajog.2022.04.015 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/85484
Title
Toward a new taxonomy of obstetrical disease: improved performance of maternal blood biomarkers for the great obstetrical syndromes when classified according to placental pathology
Author's Affiliation
Ramathibodi Hospital
Biomedical Research Institute
Inje University Paik Hospital
University of Michigan Medical School
Detroit Medical Center
Michigan State University
Soroka University Medical Center
Emek Medical Center
Hospital Dr. Sotero del Rio
University of Arizona College of Medicine – Tucson
Wayne State University School of Medicine
SKKU School of Medicine
Facultad de Medicina
Wayne State University
National Institutes of Health (NIH)
University of Ulsan College of Medicine
Biomedical Research Institute
Inje University Paik Hospital
University of Michigan Medical School
Detroit Medical Center
Michigan State University
Soroka University Medical Center
Emek Medical Center
Hospital Dr. Sotero del Rio
University of Arizona College of Medicine – Tucson
Wayne State University School of Medicine
SKKU School of Medicine
Facultad de Medicina
Wayne State University
National Institutes of Health (NIH)
University of Ulsan College of Medicine
Other Contributor(s)
Abstract
Background: The major challenge for obstetrics is the prediction and prevention of the great obstetrical syndromes. We propose that defining obstetrical diseases by the combination of clinical presentation and disease mechanisms as inferred by placental pathology will aid in the discovery of biomarkers and add specificity to those already known. Objective: To describe the longitudinal profile of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PlGF/sFlt-1 ratio throughout gestation, and to determine whether the association between abnormal biomarker profiles and obstetrical syndromes is strengthened by information derived from placental examination, eg, the presence or absence of placental lesions of maternal vascular malperfusion. Study Design: This retrospective case cohort study was based on a parent cohort of 4006 pregnant women enrolled prospectively. The case cohort of 1499 pregnant women included 1000 randomly selected patients from the parent cohort and all additional patients with obstetrical syndromes from the parent cohort. Pregnant women were classified into six groups: 1) term delivery without pregnancy complications (n=540; control); 2) preterm labor and delivery (n=203); 3) preterm premature rupture of the membranes (n=112); 4) preeclampsia (n=230); 5) small-for-gestational-age neonate (n=334); and 6) other pregnancy complications (n=182). Maternal plasma concentrations of PlGF and sFlt-1 were determined by enzyme-linked immunosorbent assays in 7560 longitudinal samples. Placental pathologists, masked to clinical outcomes, diagnosed the presence or absence of placental lesions of maternal vascular malperfusion. Comparisons between mean biomarker concentrations in cases and controls were performed by utilizing longitudinal generalized additive models. Comparisons were made between controls and each obstetrical syndrome with and without subclassifying cases according to the presence or absence of placental lesions of maternal vascular malperfusion. Results: 1) When obstetrical syndromes are classified based on the presence or absence of placental lesions of maternal vascular malperfusion, significant differences in the mean plasma concentrations of PlGF, sFlt-1, and the PlGF/sFlt-1 ratio between cases and controls emerge earlier in gestation; 2) the strength of association between an abnormal PlGF/sFlt-1 ratio and the occurrence of obstetrical syndromes increases when placental lesions of maternal vascular malperfusion are present (adjusted odds ratio [aOR], 13.6 vs 6.7 for preeclampsia; aOR, 8.1 vs 4.4 for small-for-gestational-age neonates; aOR, 5.5 vs 2.1 for preterm premature rupture of the membranes; and aOR, 3.3 vs 2.1 for preterm labor (all P<0.05); and 3) the PlGF/sFlt-1 ratio at 28 to 32 weeks of gestation is abnormal in patients who subsequently delivered due to preterm labor with intact membranes and in those with preterm premature rupture of the membranes if both groups have placental lesions of maternal vascular malperfusion. Such association is not significant in patients with these obstetrical syndromes who do not have placental lesions. Conclusion: Classification of obstetrical syndromes according to the presence or absence of placental lesions of maternal vascular malperfusion allows biomarkers to be informative earlier in gestation and enhances the strength of association between biomarkers and clinical outcomes. We propose that a new taxonomy of obstetrical disorders informed by placental pathology will facilitate the discovery and implementation of biomarkers as well as the prediction and prevention of such disorders.