Cut-off values for Gaussian first-trimester screening for early-onset preeclampsia with maternal history, biochemical markers and uterine artery Doppler.

INTRODUCTION: Several algorithms for first-trimester screening for preeclampsia are available; however, the Gaussian model algorithm is more likely to match the characteristics of different populations. It is recommended to validate a screening strategy before being implemented in clinical practice; unfortunately, the validation process might not be feasible in all settings. Thus, the aim of this study was to provide cut-off values for the Gaussian model for its use in clinical practice. MATERIAL AND METHODS: This prospective cohort study was conducted at Vall d'Hebron University Hospital (Barcelona) from October 2015 to September 2017. A total of 2641 women with singleton pregnancies were recruited. Recorded at the first-trimester scan were demographic characteristics, maternal obstetric history, maternal history, uterine artery Doppler and arterial blood pressure. Serum concentrations of pregnancy-associated plasma protein-A and placental growth factor were assessed from the first-trimester blood test. Detection rates and cut-off values for fixed 5%, 10 %, 15 %, 20 %, 25 % and 30 % false-positive rates were calculated for all combinations of markers. RESULTS: Ninety (3.41 %) of the 2641 women developed preeclampsia, which was early-onset in 11 (0.42 %). The cut-off values and their respective detection rates, for the screening of early-onset PE by all possible combinations of markers involved in this model, are provided. DISCUSSION: When external validation of first-trimester screening for preeclampsia before its clinical implementation is not feasible, the cut-off values from the Gaussian model algorithm provided in this study could be used and median values corrected prospectively if necessary.

Soluble fms-like tyrosine kinase to placental growth factor ratio in different stages of early-onset fetal growth restriction and small for gestational age.

INTRODUCTION: Increased soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF) has been demonstrated in early-onset fetal growth restriction (FGR) and small for gestational age (SGA). sFlt-1/PlGF cut-offs have been described to assess preeclampsia severity; however, sFlt-1/PlGF values present in early-onset SGA and different FGR severity stages remain unknown. Hence, the objective of this study was to describe and compare the sFlt-1/PlGF values and pregnancy outcomes among early-onset SGA/FGR stages. MATERIAL AND METHODS: This is a prospective case-control study conducted at Vall d'Hebron University Hospital. Singleton pregnancies with estimated fetal weight <10th centile and a control group of uncomplicated pregnancies between 20+0 and 31+6  weeks of gestation were enrolled. Study women were classified at diagnosis into different stages, according to estimated fetal weight centile and Doppler ultrasound. sFlt-1/PlGF serum concentrations were measured at diagnosis and, together with pregnancy outcomes, were compared among FGR severity stages, SGA, and controls. Finally, correlations between sFlt-1/PlGF values and time to delivery, gestational age at delivery, days of neonatal admission, and birthweight z-scores were investigated. RESULTS: Among the 207 women enrolled, 32 (15.4%) had uncomplicated pregnancies, 49 (23.7%) pregnancies showed SGA, and 126 (60.9%) involved FGR (92 being stage I, 17 stage II, and 17 stage III). SGA and controls had similar median sFlt-1/PlGF values (25.7 vs 27.1, P > .05) and pregnancy outcomes. However, all FGR stages had significantly poorer outcomes and greater sFlt-1/PlGF values than those of SGA and controls. Furthermore, median values differed significantly among all FGR severity stages (9.76 for stage I; 284.3 for stage II, and 625.02 for stage III, P < .05) increasing with FGR severity as well as the frequency of adverse pregnancy outcomes. Additionally, a significant correlation was found between greater sFlt-1/PlGF ratio values and gestational age at delivery, time from diagnosis to delivery, birthweight z-scores, and time in neonatal intensive care unit (r = -.637, r = -.576, r = -.161, and r = .311, respectively). CONCLUSIONS: Values of sFlt-1/PlGF at diagnosis permit early-onset FGR/SGA severity classification with good correlation with Doppler ultrasound findings and the occurrence of adverse outcomes. Thus, sFlt-1/PlGF could aid in early-onset FGR/SGA severity classification and clinical management when Doppler assessment is not feasible.

Individual risk assessment for prenatal counseling in early-onset growth-restricted and small-for-gestational-age fetuses.

INTRODUCTION: Early-onset fetal growth restriction and small-for-gestational age of fetuses lead to an increased risk of adverse pregnancy outcomes. Doppler abnormalities can predict the occurrence of complications in the short term, but normal fetal Doppler values at the time of diagnosis do not exclude their occurrence in the long term. The objective of this study was to investigate the capacity of a predictive model to assess individual risks for prenatal counseling at the time of diagnosis. MATERIAL AND METHODS: This was a prospective observational study of singleton pregnancies with estimated fetal weight below the 10th centile between 20+0 and 31+6  weeks of gestational age. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) levels, estimated fetal weight centile, uterine artery pulsatility index, fetal Doppler and maternal risk factors for placental disease were assessed at the time of enrollment. The occurrence of adverse perinatal outcomes or the need for elective delivery at <30, <34 or <37 weeks was considered an adverse pregnancy outcomes. Univariable logistic regression analysis was used to examine the association between each predictive variable and the adverse outcomes. A multivariable logistic regression-based model was constructed with the combination of all variables. An additional model without sFlt-1/PlGF was also created. Both models, and the sFlt-1/PlGF alone, were used to develop the different formulas to assess individual risks. Receiver operating characteristic curves were constructed to assess and compare their performance of screening. RESULTS: Forty-nine small-for-gestational-age fetuses and 124 with fetal growth restriction were enrolled at a median gestational age of 23.6 weeks. Elective delivery was needed in 77 (44.5%) women at <37 weeks, 53 (30.6%) women at <34 weeks and 30 (17.3%) at <30 weeks. Adverse perinatal outcomes occurred in 81 (55.9%) pregnancies. When areas under the curve were compared among models, no statistically significant differences were observed between the model with sFlt-1/PlGF and sFlt-1/PlGF alone; however, the model without sFlt-1/PlGF yielded an overall poorer performance. CONCLUSIONS: Individual risk assessment can be made at the time of early-onset fetal growth restriction/small-for-gestational-age diagnosis, which permits accurate counseling of parents with an affected fetus. Two formulas could be used: one combining maternal characteristics and ultrasound findings and the other with a single sFlt-1/PlGF measurement.