Amélie Boutin1, Cédric Gasse2, Suzanne Demers3, Geneviève Blanchet4, Yves Giguère5, Emmanuel Bujold6. 1. Reproduction, Mother, and Child Health Unit, CHU de Québec-Université Laval Research Centre, Université Laval, Québec City, QC. 2. Reproduction, Mother, and Child Health Unit, CHU de Québec-Université Laval Research Centre, Université Laval, Québec City, QC; Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Québec City, QC. 3. Reproduction, Mother, and Child Health Unit, CHU de Québec-Université Laval Research Centre, Université Laval, Québec City, QC; Department of Gynecology, Obstetrics, and Reproduction, Faculty of Medicine, Université Laval, Québec City, QC. 4. Department of Gynecology, Obstetrics, and Reproduction, Faculty of Medicine, Université Laval, Québec City, QC. 5. Reproduction, Mother, and Child Health Unit, CHU de Québec-Université Laval Research Centre, Université Laval, Québec City, QC; Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Québec City, QC. 6. Reproduction, Mother, and Child Health Unit, CHU de Québec-Université Laval Research Centre, Université Laval, Québec City, QC; Department of Gynecology, Obstetrics, and Reproduction, Faculty of Medicine, Université Laval, Québec City, QC. Electronic address: emmanuel.bujold@crchudequebec.ulaval.ca.
Abstract
OBJECTIVE: First-trimester low concentration of pregnancy-associated plasma protein A (PAPP-A) has been associated with adverse perinatal outcomes in high-risk populations. This study aimed to estimate the ability of PAPP-A to identify adverse outcomes in a low-risk population. METHODS: The study investigators recruited nulliparous women with singleton pregnancy at their 11-13-week ultrasound scan. Serum samples were collected, and maternal PAPP-A concentration was measured using the B⋅R⋅A⋅H⋅M⋅S PAPP-A KRYPTOR (ThermoFisher Scientific, Hennigsdorf, Germany) automated assay. PAPP-A was reported in multiple of median (MoM) adjusted for GA. Participants were followed until delivery for pregnancy outcomes including preeclampsia (PE), SGA <3rd percentile, and fetal death. Receiver operating characteristic curves with the area under the curve (AUC) were used to evaluate the predictive value of PAPP-A. The investigators calculated the detection rates (DRs) and positive predictive values (PPVs) of a PAPP-A < 0.4 MoM. RESULTS: The study investigators recruited 4739 eligible participants at a mean GA of 13 ± 6 weeks. The investigators observed 232 (4.9%) cases of PE, 84 (1.8%) cases of SGA, and 14 (0.3%) fetal deaths. PAPP-A was moderately associated with PE (AUC 0.57; 95% CI 0.53-0.61) and SGA (AUC 0.62; 95% CI 0.56-0.69), but not with fetal death (AUC 0.43; 95% CI 0.23-0.63). PAPP-A < 0.4 MoM was observed in 364 (7.7%) participants and had poor predictive values for PE (DR 9.8%; PPV 6.3%), SGA (DR 18.1%; PPV 4.4%), and fetal death (DR 21.4%; PPV 0.9%). CONCLUSION: Isolated first trimester PAPP-A has a limited predictive value for adverse pregnancy outcomes (other than trisomies). Low PAPP-A (<0.4 MoM) should be used in combination with other markers for the prediction of PE, SGA, or fetal death, and it does not constitute an indication for low-dose aspirin.
OBJECTIVE: First-trimester low concentration of pregnancy-associated plasma protein A (PAPP-A) has been associated with adverse perinatal outcomes in high-risk populations. This study aimed to estimate the ability of PAPP-A to identify adverse outcomes in a low-risk population. METHODS: The study investigators recruited nulliparous women with singleton pregnancy at their 11-13-week ultrasound scan. Serum samples were collected, and maternal PAPP-A concentration was measured using the B⋅R⋅A⋅H⋅M⋅S PAPP-A KRYPTOR (ThermoFisher Scientific, Hennigsdorf, Germany) automated assay. PAPP-A was reported in multiple of median (MoM) adjusted for GA. Participants were followed until delivery for pregnancy outcomes including preeclampsia (PE), SGA <3rd percentile, and fetal death. Receiver operating characteristic curves with the area under the curve (AUC) were used to evaluate the predictive value of PAPP-A. The investigators calculated the detection rates (DRs) and positive predictive values (PPVs) of a PAPP-A < 0.4 MoM. RESULTS: The study investigators recruited 4739 eligible participants at a mean GA of 13 ± 6 weeks. The investigators observed 232 (4.9%) cases of PE, 84 (1.8%) cases of SGA, and 14 (0.3%) fetal deaths. PAPP-A was moderately associated with PE (AUC 0.57; 95% CI 0.53-0.61) and SGA (AUC 0.62; 95% CI 0.56-0.69), but not with fetal death (AUC 0.43; 95% CI 0.23-0.63). PAPP-A < 0.4 MoM was observed in 364 (7.7%) participants and had poor predictive values for PE (DR 9.8%; PPV 6.3%), SGA (DR 18.1%; PPV 4.4%), and fetal death (DR 21.4%; PPV 0.9%). CONCLUSION: Isolated first trimester PAPP-A has a limited predictive value for adverse pregnancy outcomes (other than trisomies). Low PAPP-A (<0.4 MoM) should be used in combination with other markers for the prediction of PE, SGA, or fetal death, and it does not constitute an indication for low-dose aspirin.