M Fiolna1,2, M Machuca1,2, T Karampitsakos1,2, R Akolekar1,3, K H Nicolaides2. 1. Fetal Medicine Unit, Medway Maritime Hospital, Gillingham, UK. 2. Fetal Medicine Research Institute, King's College Hospital, London, UK. 3. Institute of Medical Sciences, Canterbury Christ Church University, Chatham, UK.
Abstract
OBJECTIVE: To investigate the additive value of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), measured within 24 h prior to induction of labor, to the performance of screening for adverse perinatal outcome provided by maternal risk factors and the cerebroplacental ratio (CPR). METHODS: This was a prospective observational study of 795 singleton pregnancies undergoing induction of labor at ≥ 37 weeks' gestation. Before induction of labor, Doppler ultrasound was used to measure the pulsatility index (PI) in the umbilical artery (UA) and fetal middle cerebral artery (MCA) and maternal blood was obtained for measurement of serum PlGF and sFlt-1. The measured UA-PI, MCA-PI and their ratio (CPR) were converted to multiples of the median (MoM) after adjustment for gestational age, and the measured PlGF and sFlt-1 were converted to MoM after adjustment for gestational age, maternal characteristics and the machine used for the assays. Univariable and multivariable logistic regression analysis was used to determine factors that provided a significant contribution in the prediction of adverse perinatal outcome, defined as the presence of any one of Cesarean section for non-reassuring fetal status in labor, umbilical arterial or venous cord blood pH ≤ 7 and ≤ 7.1, respectively, 5-min Apgar score < 7 or admission to the neonatal intensive care unit for ≥ 24 h. The detection rate (DR) and false-positive rate (FPR) in screening for adverse perinatal outcome were determined. RESULTS: In pregnancies with adverse perinatal outcome, compared to those without, median serum PlGF MoM was lower (0.44; interquartile range (IQR), 0.30-0.82 vs 0.60; IQR, 0.36-1.07; P = 0.003), but median sFlt-1 MoM was not significantly different (P = 0.080). Multivariable regression analysis demonstrated that, in the prediction of adverse perinatal outcome, there was significant contribution from maternal risk factors and CPR MoM but not PlGF MoM or sFlt-1 MoM. The performance of screening for adverse perinatal outcome achieved by maternal risk factors alone (DR of 28.9% at FPR of 10%) was not improved by the addition of CPR (DR of 33.8% at FPR of 10%) (area under the curve, 0.702; 95% CI, 0.654-0.750 vs 0.712; 95% CI, 0.664-0.760; P = 0.233). CONCLUSION: Serum PlGF and sFlt-1, measured within 24 h prior to induction of labor, do not provide a significant additional contribution to maternal risk factors in the prediction of adverse perinatal outcome.
OBJECTIVE: To investigate the additive value of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), measured within 24 h prior to induction of labor, to the performance of screening for adverse perinatal outcome provided by maternal risk factors and the cerebroplacental ratio (CPR). METHODS: This was a prospective observational study of 795 singleton pregnancies undergoing induction of labor at ≥ 37 weeks' gestation. Before induction of labor, Doppler ultrasound was used to measure the pulsatility index (PI) in the umbilical artery (UA) and fetal middle cerebral artery (MCA) and maternal blood was obtained for measurement of serum PlGF and sFlt-1. The measured UA-PI, MCA-PI and their ratio (CPR) were converted to multiples of the median (MoM) after adjustment for gestational age, and the measured PlGF and sFlt-1 were converted to MoM after adjustment for gestational age, maternal characteristics and the machine used for the assays. Univariable and multivariable logistic regression analysis was used to determine factors that provided a significant contribution in the prediction of adverse perinatal outcome, defined as the presence of any one of Cesarean section for non-reassuring fetal status in labor, umbilical arterial or venous cord blood pH ≤ 7 and ≤ 7.1, respectively, 5-min Apgar score < 7 or admission to the neonatal intensive care unit for ≥ 24 h. The detection rate (DR) and false-positive rate (FPR) in screening for adverse perinatal outcome were determined. RESULTS: In pregnancies with adverse perinatal outcome, compared to those without, median serum PlGF MoM was lower (0.44; interquartile range (IQR), 0.30-0.82 vs 0.60; IQR, 0.36-1.07; P = 0.003), but median sFlt-1 MoM was not significantly different (P = 0.080). Multivariable regression analysis demonstrated that, in the prediction of adverse perinatal outcome, there was significant contribution from maternal risk factors and CPR MoM but not PlGF MoM or sFlt-1 MoM. The performance of screening for adverse perinatal outcome achieved by maternal risk factors alone (DR of 28.9% at FPR of 10%) was not improved by the addition of CPR (DR of 33.8% at FPR of 10%) (area under the curve, 0.702; 95% CI, 0.654-0.750 vs 0.712; 95% CI, 0.664-0.760; P = 0.233). CONCLUSION: Serum PlGF and sFlt-1, measured within 24 h prior to induction of labor, do not provide a significant additional contribution to maternal risk factors in the prediction of adverse perinatal outcome.