title: Diagnostic accuracy of maternal serum macrophage inhibitory cytokine-1 and pregnancy-associated plasma protein-A at 6-10 weeks of gestation to predict miscarriage.
abstract: OBJECTIVE
  To determine whether serum macrophage inhibitory cytokine-1, pregnancy-associated plasma protein-A (PAPP-A), anandamide, or β-human chorionic gonadotropin (hCG) measured in an asymptomatic population in the middle of the first trimester with a viable fetus predicts subsequent miscarriage.
  
  
  METHODS
  We undertook a prospective cohort study at Mercy Hospital for Women between 2004 and 2008. Participants (N=782) were recruited from prenatal clinics, where samples were taken from asymptomatic women at 6 0/7 to 10 6/7 weeks of gestation. We collected samples from only those women for whom we were able to obtain ultrasound evidence of a singleton with fetal cardiac activity. Serum macrophage inhibitory cytokine-1, PAPP-A, anandamide, and β-hCG concentrations were assayed.
  
  
  RESULTS
  Twenty-one (2.7%) miscarried and 761 did not. Among those who miscarried, macrophage inhibitory cytokine-1 and PAPP-A were significantly decreased at 63% (multiples of the median (MOM) 0.63, 25th-75th percentiles 0.33-0.88) and 23% (MOM 0.23, 25th-75th percentiles 0.12-0.48) of levels seen among those with ongoing pregnancies (P<.001 for both comparisons). In contrast, neither serum β-hCG (MOM 0.99, 25th-75th percentiles 0.46-1.86) nor anandamide (MOM 1.07, 25th-75th percentiles 0.87-1.19) was elevated or decreased among those who miscarried compared with those with ongoing pregnancies. At a fixed 10% false-positive rate (90% specificity), a test combining macrophage inhibitory cytokine-1 and PAPP-A yielded 63% sensitivity and a 6.6 positive likelihood ratio in predicting miscarriage.
  
  
  CONCLUSIONS
  Low serum levels of macrophage inhibitory cytokine-1 and PAPP-A measured from asymptomatic women at 6-10 weeks of gestation with viable pregnancies can predict subsequent miscarriage. These analytes are likely to have an important biological role in early pregnancy and are likely to be useful clinical biomarkers for miscarriage and other early pregnancy complications.
  
  
  METHODS
  II.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia. stong@unimelb.edu.au
authors.forename: Stephen
authors.initials: S
authors.lastname: Tong
authors.forename: Gene-Lyn
authors.initials: GL
authors.lastname: Ngian
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Onwude
authors.forename: Michael
authors.initials: M
authors.lastname: Permezel
authors.forename: Burcu
authors.initials: B
authors.lastname: Saglam
authors.forename: Sarah
authors.initials: S
authors.lastname: Hay
authors.forename: Justin C
authors.initials: JC
authors.lastname: Konje
authors.forename: Tim H
authors.initials: TH
authors.lastname: Marczylo
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Fleming
authors.forename: Susan P
authors.initials: SP
authors.lastname: Walker
authors.forename: Martha
authors.initials: M
authors.lastname: Lappas
mesh_terms: D000022:Abortion, Spontaneous / Q000097:blood / Q000175:diagnosis*; D000328:Adult; D001095:Arachidonic Acids / Q000097:blood; D015415:Biomarkers / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D063388:Endocannabinoids; D005189:False Positive Reactions; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D053284:Polyunsaturated Alkamides / Q000097:blood; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011446:Prospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity
chemical_list: D001095:Arachidonic Acids; D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D063388:Endocannabinoids; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D053284:Polyunsaturated Alkamides; D011266:Pregnancy-Associated Plasma Protein-A; C078814:anandamide