title: Prediction of small-for-gestational-age neonates: screening by maternal serum biochemical markers at 19-24 weeks.
abstract: OBJECTIVE
  To investigate the value of maternal serum concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (β-hCG) and α-fetoprotein (AFP) at 19-24 weeks' gestation, in combination with maternal factors and fetal biometry, in the prediction of delivery of small-for-gestational-age (SGA) neonates, in the absence of pre-eclampsia (PE) and examine the potential value of such assessment in deciding whether the third-trimester scan should be performed at 32 and/or 36 weeks' gestation.
  
  
  METHODS
  This was a screening study in 9715 singleton pregnancies, including 481 (5.0%) that delivered SGA neonates with birth weight < 5(th) percentile (SGA < 5(th) ), in the absence of PE. Multivariable logistic regression analysis was used to determine if screening by a combination of maternal factors, Z-scores of fetal head circumference, abdominal circumference and femur length, and log10 multiples of the median (MoM) values of PlGF, sFlt-1, PAPP-A, free β-hCG or AFP had a significant contribution to the prediction of SGA neonates. A model was developed in selecting the gestational age for third-trimester assessment, at 32 and/or 36 weeks, based on the results of screening at 19-24 weeks.
  
  
  RESULTS
  Compared to the normal group, the mean log10 MoM value of PlGF was lower, AFP was higher and sFlt-1, PAPP-A and free β-hCG were not significantly different in the SGA < 5(th) group that delivered < 37 weeks. The detection rate (DR) of combined screening by maternal factors, fetal biometry and serum PlGF and AFP at 19-24 weeks was 100%, 76% and 38% for SGA < 5(th) delivering < 32, 32-36 and ≥ 37 weeks' gestation, respectively, at a false-positive rate (FPR) of 10%. In a hypothetical model, it was estimated that, if the desired objective of prenatal screening is to predict about 80% of the cases of SGA < 5(th) , it would be necessary to select 11% of the population at the 19-24-week assessment to be reassessed at 32 weeks and 46% to be reassessed at 36 weeks; 54% would not require a third-trimester scan.
  
  
  CONCLUSIONS
  Prenatal prediction of a high proportion of SGA neonates necessitates the undertaking of screening in the third trimester of pregnancy, in addition to assessment in the second trimester, and the timing of such screening, at 32 and/or 36 weeks, should be contingent on the results of the assessment at 19-24 weeks.
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Lesmes
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Gallo
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Gonzalez
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: L C
authors.initials: LC
authors.lastname: Poon
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: K H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003661:Decision Support Techniques; D005189:False Positive Reactions; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D016015:Logistic Models; D062145:Maternal Serum Screening Tests; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood*; D011446:Prospective Studies; D012372:ROC Curve
chemical_list: D015415:Biomarkers
keywords: free β-human chorionic gonadotropin; placental growth factor; pre-eclampsia; pregnancy-associated plasma protein-A; pyramid of antenatal care; second-trimester screening; small-for-gestational age; soluble fms-like tyrosine kinase-1; α-fetoprotein