Maternal serum placental growth factor (PlGF) in small for gestational age pregnancy at 11(+0) to 13(+6) weeks of gestation.

To investigate the pathogenesis of pregnancies delivering small for gestational age (SGA) neonates by examining biochemical and Doppler indices of placental development during the first trimester of pregnancy. The concentration of placental growth factor (PlGF) at 11(+0)-13(+6) weeks was measured in 296 cases, which delivered SGA neonates, and 609 controls. The newborn was considered to be SGA if the birth weight was less than the fifth percentile after correction for gestation at delivery and sex, maternal racial origin, weight, height and parity. The distributions of uterine artery pulsatility index (PI), PlGF and PAPP-A, expressed in multiples of the median (MoM), in the control and SGA groups were compared. Logistic regression analysis was used to determine if significant contribution is provided by maternal factors, PlGF, PAPP-A and uterine artery PI in predicting SGA. The median PlGF (0.900 MoM) and PAPP-A (0.778 MoM) were lower and uterine artery PI was higher (1.087 MoM) in the SGA group than in the controls (PlGF: 0.991 MoM; PAPP-A: 1.070 MoM; uterine artery PI: 1.030 MoM). In the SGA group there was a significant association between PlGF and PAPP-A (r = 0.368, p < 0.0001) and uterine artery PI (r = 0.191, p = 0.001). Significant contributions for the prediction of SGA were provided by maternal factors, PlGF and PAPP-A and with combined screening the detection rate was 27% at a false-positive rate of 5%. Birth weight is predetermined by placental development during the first trimester of pregnancy.

Poon LC ，Zaragoza E ，Akolekar R ，Anagnostopoulos E ，Nicolaides KH ... -  《PRENATAL DIAGNOSIS》

Prediction of small-for-gestational-age neonates: screening by biophysical and biochemical markers at 30-34 weeks.

To investigate the potential value of combined screening by maternal characteristics and medical history (maternal factors), estimated fetal weight (EFW), uterine artery pulsatility index (UtA-PI), mean arterial pressure (MAP) and serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) at 30-34 weeks' gestation in the prediction of delivery of small-for-gestational-age (SGA) neonates, in the absence of pre-eclampsia (PE). This was a screening study in 9472 singleton pregnancies at 30-34 weeks' gestation, comprising 469 that delivered SGA neonates and 9003 cases unaffected by SGA, PE or gestational hypertension. Multivariable logistic regression analysis was used to determine if UtA-PI, MAP and serum PlGF or sFlt-1, individually or in combination, improved the prediction of SGA neonates provided from screening by maternal factors and EFW. Compared to the normal group, mean log10 multiples of the median (MoM) values of UtA-PI, MAP and serum sFlt-1 were significantly higher and log10 MoM PlGF was lower in the SGA group. Multivariable logistic regression analysis demonstrated that in the prediction of SGA neonates with a birth weight < 5(th) percentile, delivering < 5 weeks and ≥ 5 weeks after assessment, there were significant independent contributions from maternal factors, EFW, UtA-PI, MAP, and serum PlGF and sFlt-1, but the best performance was provided by a combination of maternal factors, EFW, UtA-PI, MAP and serum PlGF, excluding sFlt-1. Combined screening predicted, at a 10% false-positive rate, 89%, 94%, 96% of SGA neonates delivering at 32-36 weeks' gestation with birth weight < 10(th) , < 5(th) and < 3(rd) percentiles, respectively; the respective detection rates of combined screening for SGA neonates delivering ≥ 37 weeks were 57%, 65% and 72%. Combined screening by maternal factors and biophysical and biochemical markers at 30-34 weeks' gestation could identify a high proportion of pregnancies that will deliver SGA neonates.

Bakalis S ，Peeva G ，Gonzalez R ，Poon LC ，Nicolaides KH ... -  《-》

Maternal serum placental growth factor at 11 + 0 to 13 + 6 weeks of gestation in the prediction of pre-eclampsia.

To investigate the potential value of maternal serum placental growth factor (PlGF) in first-trimester screening for pre-eclampsia (PE). The concentration of PlGF at 11 + 0 to 13 + 6 weeks' gestation was measured in samples from 127 pregnancies that developed PE, including 29 that required delivery before 34 weeks (early PE) and 98 with late PE, 88 cases of gestational hypertension (GH) and 609 normal controls. The distributions of PlGF multiples of the median (MoM) in the control and hypertensive groups were compared. Logistic regression analysis was used to determine the factors with a significant contribution for predicting PE. In the control group significant independent contributions for log PlGF were provided by fetal crown-rump length, maternal weight, cigarette smoking and racial origin, and after correction for these variables the median MoM PlGF was 0.991. In the early-PE and late-PE groups PlGF (0.611 MoM and 0.822 MoM, respectively; P < 0.0001) and pregnancy-associated plasma protein-A (PAPP-A) (0.535 MoM; P < 0.0001 and 0.929 MoM; P = 0.015, respectively) were reduced but in GH (PlGF: 0.966 MoM; PAPP-A: 0.895 MoM) there were no significant differences from controls. Significant contributions for the prediction of PE were provided by maternal characteristics and obstetric history, serum PlGF and uterine artery pulsatility index (PI) and with combined screening the detection rates for early PE and late PE were 90% and 49%, respectively, for a false-positive rate of 10%. Effective screening for PE can be provided by a combination of maternal characteristics and obstetric history, uterine artery PI and maternal serum PlGF at 11 + 0 to 13 + 6 weeks' gestation.

Akolekar R ，Zaragoza E ，Poon LC ，Pepes S ，Nicolaides KH ... -  《-》

Prediction of small-for-gestational-age neonates: screening by maternal biochemical markers at 30-34 weeks.

To investigate the potential value of serum 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 30-34 weeks' gestation in the prediction of delivery of small-for-gestational-age (SGA) neonates, in the absence of pre-eclampsia (PE). This was a screening study in singleton pregnancies at 30-34 weeks' gestation, including 490 that delivered SGA neonates and 9360 cases that were unaffected by SGA, PE or gestational hypertension (normal outcome). Multivariable logistic regression analysis was used to determine if screening by serum PlGF, sFlt-1, PAPP-A, free β-hCG and AFP, individually or in combination, improved the prediction of SGA neonates provided by screening with maternal characteristics and medical history (maternal factors), and estimated fetal weight (EFW) from fetal head circumference, abdominal circumference and femur length. Compared to the normal group, the mean log10 multiples of the median (MoM) values of PlGF and AFP were significantly lower and the mean log10 MoM values of sFlt-1 and free β-hCG were significantly higher in the SGA group with a birth weight < 5(th) percentile (SGA < 5(th)) delivering < 5 weeks following assessment. The best model for prediction of SGA was provided by a combination of maternal factors, EFW and serum PlGF. Such combined screening, predicted, at a 10% false-positive rate, 85%, 93% and 92% of SGA neonates delivering < 5 weeks following assessment with birth weight < 10(th), < 5(th) and < 3(rd) percentiles, respectively; the respective detection rates of combined screening for SGA neonates delivering ≥ 5 weeks following assessment were 57%, 64% and 71%. Combined screening by maternal factors, EFW and serum PlGF at 30-34 weeks' gestation can identify a high proportion of pregnancies that subsequently deliver SGA neonates.

Bakalis S ，Gallo DM ，Mendez O ，Poon LC ，Nicolaides KH ... -  《-》

Prediction of small-for-gestational-age neonates: screening by maternal serum biochemical markers at 19-24 weeks.

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. 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. 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. 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.

Lesmes C ，Gallo DM ，Gonzalez R ，Poon LC ，Nicolaides KH ... -  《-》