First-trimester biochemical markers of aneuploidy and the prediction of small-for-gestational age fetuses.
OBJECTIVE
To examine the clinical utility of the first-trimester biochemical markers of aneuploidy in their ability to predict subsequent delivery of a small-for-gestational age (SGA) infant.


METHODS
We examined 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 expected normal median (MoM) for a pregnancy of the same gestation. The association between free beta-hCG and PAPP-A and the incidence of SGA were assessed by comparing the relative incidence at MoM cut-offs and birth-weight centile cut-offs. At various marker levels the likelihood ratios (LR) for SGA were also calculated after excluding other adverse pregnancy complications.


RESULTS
There were 46,262 pregnancies resulting in live births with birth weight at or above the 10(th) centile, and 3,539 below the 10(th) centile for gestation (SGA). There was a significant inverse association between the risk for SGA and maternal serum PAPP-A MoM but not free beta-hCG MoM. At the 5(th) centile of the normal outcome group for PAPP-A (0.415 MoM) the odds ratios for SGA below the 10(th), 5(th) and 3(rd) centiles of normal were 2.70, 3.21 and 3.66 and the respective detection rates for SGA were 12.0%, 14.0% and 16.0%.


CONCLUSIONS
Low levels of maternal serum PAPP-A are associated, in the absence of an abnormal karyotype, with an increased risk for subsequent delivery of an SGA infant.
Spencer
K
K
Prenatal Screening Unit, Clinical Biochemistry Department, Harold Wood Hospital, Romford, Essex, UK. KevinSpencer1@aol.com
Cowans
N J
NJ
Avgidou
K
K
Molina
F
F
Nicolaides
K H
KH
D000328:Adult; D000782:Aneuploidy; D015415:Biomarkers / Q000378:metabolism; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D048208:Nuchal Translucency Measurement / Q000379:methods; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First / Q000378:metabolism; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011296:Prenatal Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity
D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A