First-trimester ultrasound and biochemical markers of aneuploidy and the prediction of preterm or early preterm delivery

Objectives: To examine the clinical utility of the first-trimester markers of aneuploidy in their ability to predict preterm delivery.

Methods: We examined 54 722 singleton pregnancies with no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted to multiples of the median (MoM) of the expected normal median for a pregnancy of the same gestation and the measurements of fetal NT were expressed as the difference (delta) from the normal median NT for crown-rump length. The association between free beta-hCG, PAPP-A and delta NT and the incidence of preterm delivery before 37 weeks or early preterm delivery before 34 weeks was assessed by comparing the relative incidence at a number of MoM or delta NT cut-offs and at various centile cut-offs. At various marker levels the likelihood ratios (LR) for preterm delivery and early preterm delivery were also calculated after excluding other adverse pregnancy complications.

Results: The risk of preterm delivery increased with decreasing maternal serum PAPP-A. In the 3132 cases delivering before 37 weeks the PAPP-A MoM was 0.91 and in the 1060 cases delivering before 34 weeks the PAPP-A MoM was 0.90. At the 5th centile of the normal outcome group for PAPP-A (0.415 MoM) the odds ratios for delivery before 37 weeks and before 34 weeks were 1.92 and 2.35, respectively. The respective values for the 5th centile of free beta-hCG (0.41 MoM) were 1.18 and 1.08 and for the 95th centile of delta NT they were 0.91 and 0.77, respectively.

Conclusions: Low levels of maternal serum PAPP-A are associated, in the absence of an abnormal karyotype, with an increased risk of preterm or early preterm delivery. The LR profiles provided at various levels of PAPP-A may be of some help in counseling women with such results and may raise awareness among healthcare professionals for increased surveillance in such cases.