Prediction of macrosomia at birth in type-1 and 2 diabetic pregnancies with biomarkers of early placentation

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).

Design: Nested case-control study.

Setting: Routine first-trimester combined test.

Population: 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.

Main outcome measures: 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.