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 ... -  《-》

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 biophysical and biochemical markers at 19-24 weeks.

To investigate the value of combined screening by maternal characteristics and medical history, fetal biometry and biophysical and biochemical markers at 19-24 weeks' gestation, for 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 at 32 and/or 36 weeks' gestation. This was a screening study in 7816 singleton pregnancies, including 389 (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, fetal biometry, uterine artery pulsatility index (UtA-PI) and maternal serum concentrations of placental growth factor (PlGF) and α-fetoprotein (AFP) had significant contribution in predicting SGA neonates. A model was developed for selecting the gestational age for third-trimester assessment, at 32 and/or 36 weeks, based on the results of screening at 19-24 weeks. Significant independent contributions to the prediction of SGA < 5(th) were provided by maternal factors, fetal biometry, UtA-PI and serum PlGF and AFP. The detection rate (DR) of such combined screening at 19-24 weeks was 100%, 78% and 42% for SGA < 5(th) delivering < 32, at 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 44% to be reassessed at 36 weeks; 57% 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.

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

Prediction of small-for-gestational-age neonates: screening by placental growth factor and soluble fms-like tyrosine kinase-1 at 35-37 weeks.

To investigate the potential value of maternal serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) at 35-37 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 35-37 weeks, including 158 that delivered SGA neonates with birth weight < 5(th) percentile and 3701 cases unaffected by SGA, PE or gestational hypertension. Multivariable logistic regression analysis was used to determine if measuring serum levels of PlGF and sFlt-1 improved the prediction of delivery 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 median PlGF multiples of the median (MoM) was significantly lower and the median sFlt-1 MoM was significantly higher in the SGA group. Combined screening by maternal factors and EFW at 35-37 weeks predicted, at 10% false-positive rate (FPR), 90%, 92% and 94% of SGA neonates with birth weight < 10(th), < 5(th) and < 3(rd) percentiles, respectively, delivering < 2 weeks following assessment; the respective values for SGA delivering ≥ 37 weeks were 66%, 73% and 80%. When PlGF and sFlt-1 were added to a model that combines maternal factors and EFW, sFlt-1 did not remain as a significant independent predictor of SGA < 5(th). Combined screening by maternal factors, EFW and serum PlGF, predicted, at a 10% FPR, 88%, 96% and 94% of SGA neonates with birth weight < 10(th), < 5(th) and < 3(rd) percentiles, respectively, delivering < 2 weeks following assessment and the respective values for SGA delivering ≥ 37 weeks were 64%, 75% and 80%. sFlt-1 does not provide significant independent prediction of SGA, in the absence of PE, in addition to combined testing by maternal factors and fetal biometry at 35-37 weeks; whilst the addition of PlGF alone marginally improves the performance of screening.

Fadigas C ，Peeva G ，Mendez O ，Poon LC ，Nicolaides KH ... -  《-》

Biophysical and biochemical markers at 30-34 weeks' gestation in the prediction of adverse perinatal outcome.

To investigate the potential value of biophysical and biochemical markers at 30-34 weeks' gestation in the prediction of adverse perinatal outcome. This was a screening study in 8268 singleton pregnancies at 30-34 weeks' gestation. Estimated fetal weight (EFW), uterine artery (UtA) pulsatility index (PI), umbilical artery (UA) PI, fetal middle cerebral artery (MCA) PI, mean arterial pressure (MAP), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured. The detection rate (DR) and false-positive rate (FPR) of screening by each biomarker were estimated for stillbirth, pre-eclampsia, delivery of small-for-gestational-age (SGA) neonate, Cesarean section for fetal distress before or during labor, umbilical arterial cord blood pH ≤7.0 or umbilical venous cord blood pH ≤7.1, 5-min Apgar score < 7 and admission to the neonatal unit (NNU). Multivariable regression analysis demonstrated that significant prediction of PE was provided by PlGF, sFlt-1, MAP and MCA-PI, with a DR of 98% for PE delivering < 37 weeks' gestation and 56% for those delivering ≥ 37 weeks, at a 10% FPR. Prediction of SGA was provided by EFW, PlGF, sFlt-1, UtA-PI, UA-PI and MCA-PI, with a DR of 88% for SGA delivering < 37 and 51% for those delivering ≥ 37 weeks' gestation, at a 10% FPR. Prediction of stillbirth was provided by EFW, UtA-PI and MCA-PI, with DR of 30% at 10% FPR. Prediction of Cesarean section for fetal distress before labor was provided by EFW, sFlt-1, UtA-PI and UA-PI, with a DR of 90% at a 10% FPR. Prediction of fetal distress in labor was provided by EFW and sFlt-1, with a DR of 16% at a 10% FPR. There were no significant differences from the normal outcome group in any of the biomarkers for low cord blood pH, low Apgar score or NNU admission for cases other than those with PE and/or SGA. At 30-34 weeks' gestation, biomarkers of impaired placentation and fetal hypoxemia provide good prediction of PE, SGA and fetal distress before labor, but poor or no prediction of stillbirth and adverse events in labor or after birth.

Valiño N ，Giunta G ，Gallo DM ，Akolekar R ，Nicolaides KH ... -  《-》