Maternal Early Pregnancy Serum Metabolomics Profile and Abnormal Vaginal Bleeding as Predictors of Placental Abruption: A Prospective Study.
OBJECTIVE
Placental abruption, an ischemic placental disorder, complicates about 1 in 100 pregnancies, and is an important cause of maternal and perinatal morbidity and mortality worldwide. Metabolomics holds promise for improving the phenotyping, prediction and understanding of pathophysiologic mechanisms of complex clinical disorders including abruption. We sought to evaluate maternal early pregnancy pre-diagnostic serum metabolic profiles and abnormal vaginal bleeding as predictors of abruption later in pregnancy.


METHODS
Maternal serum was collected in early pregnancy (mean 16 weeks, range 15 to 22 weeks) from 51 abruption cases and 51 controls. Quantitative targeted metabolic profiles of serum were acquired using electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and the Absolute IDQ® p180 kit. Maternal sociodemographic characteristics and reproductive history were abstracted from medical records. Stepwise logistic regression models were developed to evaluate the extent to which metabolites aid in the prediction of abruption. We evaluated the predictive performance of the set of selected metabolites using a receiver operating characteristics (ROC) curve analysis and area under the curve (AUC).


RESULTS
Early pregnancy vaginal bleeding, dodecanoylcarnitine/dodecenoylcarnitine (C12 / C12:1), and phosphatidylcholine acyl-alkyl C 38:1 (PC ae C38:1) strongly predict abruption risk. The AUC for these metabolites alone was 0.68, for early pregnancy vaginal bleeding alone was 0.65, and combined the AUC improved to 0.75 with the addition of quantitative metabolite data (P = 0.003).


CONCLUSIONS
Metabolomic profiles of early pregnancy maternal serum samples in addition to the clinical symptom, vaginal bleeding, may serve as important markers for the prediction of abruption. Larger studies are necessary to corroborate and validate these findings in other cohorts.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.
Bizu
B
Gelaye
Discovery Sciences, RTI International, Research Triangle Park, NC, United States of America.
Susan J
SJ
Sumner
Discovery Sciences, RTI International, Research Triangle Park, NC, United States of America.
Susan
S
McRitchie
Discovery Sciences, RTI International, Research Triangle Park, NC, United States of America.
James E
JE
Carlson
Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York, NY, United States of America.|Department of Epidemiology, Joseph L. Mailman School of Public Health, Columbia University, New York, NY, United States of America.
Cande V
CV
Ananth
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States of America.|Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, United States of America.
Daniel A
DA
Enquobahrie
Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, United States of America.
Chunfang
C
Qiu
Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, United States of America.
Tanya K
TK
Sorensen
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.
Michelle A
MA
Williams
D000037:Abruptio Placentae / Q000097:blood* / Q000209:etiology* / Q000378:metabolism; D000328:Adult; D005260:Female; D006801:Humans; D055442:Metabolome; D055432:Metabolomics; D016017:Odds Ratio; D011247:Pregnancy; D011446:Prospective Studies; D012372:ROC Curve; D014592:Uterine Hemorrhage / Q000097:blood* / Q000150:complications* / Q000378:metabolism