title: Prediction of macrosomia at birth in type-1 and 2 diabetic pregnancies with biomarkers of early placentation.
abstract: OBJECTIVE
  To evaluate the value of first trimester placental biomarkers (fβ-hCG, PAPP-A, ADAM12, PP13 and PlGF) and fetal nuchal translucency (NT) in the prediction of macrosomia at birth in pregestational type-1 and type-2 diabetes (PGDM).
  
  
  METHODS
  Nested case-control study.
  
  
  METHODS
  Routine first-trimester combined test.
  
  
  METHODS
  A total of 178 PGDM and 186 control pregnancies.
  
  
  METHODS
  ADAM12, PP13 and PlGF concentrations were measured in stored first-trimester serum, previously tested for fβ-hCG and PAPP-A. All concentrations were expressed as multiples of the median (MoM). Where applicable, the median MoMs of PGDM and control pregnancies were compared in relation to birthweight centiles (≤90th centile, non-macrosomic, versus >90th centile, macrosomic). Model-predicted detection rates for fixed false-positive rates were obtained for statistically significant markers, separately and in combination.
  
  
  METHODS
  Prediction of macrosomia in diabetic pregnancies.
  
  
  RESULTS
  In the PGDM group, median ADAM12 MoM (0.88; P = 0.007) was lower than in the controls. Subgroup analyses showed that median MoMs of PAPP-A (0.65), ADAM12 (0.85), PP13 (0.81) and PlGF (0.91) were only reduced in the PGDM non-macrosomic birthweight subgroup (n = 93) compared with other weight subgroups. In the PGDM macrosomic birthweight subgroup (n = 69), MoMs of all markers were comparable with the control birthweight subgroups. The screening performance for macrosomia at birth in the PGDM group provided a detection rate of 30% for a 5% false-positive rate (FPR) and 43% for a 10% FPR.
  
  
  CONCLUSIONS
  Macrosomia at birth in PGDM pregnancies may be predicted by normal levels of PAPP-A, ADAM12, PP13 and PlGF already in the first trimester of pregnancy. Fetal birthweight in PGDM offspring is partially determined by placental development during the first trimester of pregnancy. The present increase in fetal macrosomia may be related to better early glycemic control and placentation.
authors.affiliation: Laboratory for Infectious Diseases and Screening, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. sylwia.kuc@rivm.nl
authors.forename: S
authors.initials: S
authors.lastname: Kuc
authors.forename: E J
authors.initials: EJ
authors.lastname: Wortelboer
authors.forename: M P H
authors.initials: MP
authors.lastname: Koster
authors.forename: H W
authors.initials: HW
authors.lastname: de Valk
authors.forename: P C J I
authors.initials: PC
authors.lastname: Schielen
authors.forename: G H A
authors.initials: GH
authors.lastname: Visser
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072199:ADAM12 Protein; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D005320:Fetal Macrosomia / Q000175:diagnosis*; D037161:Galectins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D010929:Placentation / Q000502:physiology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism; D011261:Pregnancy Trimester, First; D011254:Pregnancy in Diabetics; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D011296:Prenatal Diagnosis / Q000379:methods*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D037161:Galectins; C038195:LGALS13 protein, human; D008565:Membrane Proteins; C098069:PIGF protein, human; D011257:Pregnancy Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D011266:Pregnancy-Associated Plasma Protein-A