Background Fetal growth restriction, i.e. the restriction of genetically predetermined growth potential due to placental dysfunction, is a major cause of neonatal morbidity and mortality. The consequences of inadequate fetal growth can be life-long, but the risks can be reduced substantially if the condition is identified prenatally. Currently, screening strategies are based on ultrasound detection of a small-for-gestational age fetus and do not take into account the underlying vascular pathology in the placenta. Measurement of maternal circulating angiogenic biomarkers placental growth factor, sFlt-1 (soluble FMS-like tyrosine kinase-1) are increasingly used in studies on fetal growth restriction as they reflect the pathophysiological process in the placenta. However, interpretation of the role of angiogenic biomarkers in prediction of fetal growth restriction is hampered by the varying design, population, timing, assay technique and cut-off values used in these studies. Methods We conducted a systematic-review in PubMed (MEDLINE), EMBASE (Ovid) and Cochrane to explore the predictive performance of maternal concentrations of placental growth factor, sFlt-1 and their ratio for fetal growth restriction and small-for-gestational age, at different gestational ages, and describe the longitudinal changes in biomarker concentrations and optimal discriminatory cut-off values. Results We included 26 studies with 2514 cases with small-for-gestational age, 27 cases of fetal growth restriction, 582 cases mixed small-for-gestational age/fetal growth restriction and 29,374 reference. The largest mean differences for the two biomarkers and their ratio were found after 26 weeks of gestational age and not in the first trimester. The ROC-AUC varied between 0.60 and 0.89 with sensitivity and specificity matching the different cut-off values or a preset false-positive rate of 10%. Conclusions Most of the studies did not make a distinction between small-for-gestational age and fetal growth restriction, and therefore the small-for-gestational age group consists of fetuses with growth restriction and fetuses that are constitutionally normal. The biomarkers can be a valuable screening tool for small-for-gestational age pregnancies, but unfortunately, there is not yet a clear cut-off value to use for screening. More research is needed to see if these biomarkers are sufficiently able to differentiate growth restriction on their own and how these biomarkers in combination with other relevant clinical and ultrasound parameters can be used in clinical routine diagnostics.

in the first trimester. We aimed to explore pregnancy outcomes in women with a positive PE screening test using the Fetal Medicine Foundation (FMF) algorithm. Methods: We conducted a prospective cohort study of Canadian pregnant women with singleton fetus recruited at 11-14 weeks. Lethal anomalies and medical termination of pregnancies were excluded. Maternal age, body mass index, methods of conception, personal history of PE, ethnicity, mean arterial blood pressure, PAPP-A, PlGF and mean uterine artery pulsatility index were submitted into the online FMF algorithm. Simple imputation was used for the treatment of missing values. Pregnancy outcomes, including PE, small for gestational age (SGA) <3rd centile and fetal death, were reported for women with a positive preterm PE screening test (≥1/70) and compared to women with a negative (<1/70) screening test. Results: We included 6067 participants, including 672 (11%) with a positive FMF screening test. The latter were at greater risk of PE (13.4% vs. 3.4%), preterm PE (3.7% vs. 0.3%), PE<34 weeks (1.3% vs. 0.09%), SGA<3rd centile (4.1% vs. 1.4%), preterm SGA<3rd centile (0.7% vs. 0.04%), fetal death (1.2% vs. 0.4%; p=0.004), miscarriage at 14-20 weeks (0.6% vs. 0.2%; p=0.04), or any of the above complications (16.8% vs. 5.0%) than women with negative screening test (all with p<0.0001, except if otherwise specified). Thirty (4.5%) women with a positive test developed one of the severe complications (preterm PE, preterm SGA, fetal death) compared to 31 (0.6%) women with a negative screening test (p<0.0001) after exclusion of miscarriages. Conclusions: Women with a first-trimester positive FMF preterm PE screening test are at high-risk of severe pregnancy complications that are preventable with low-dose aspirin in early pregnancy. OP17.04Predictive value of serial sFlt-1, PlGF and sFlt-1/PlGF ratio measurement in predicting the development of placental syndrome in women at high risk: a pilot study Objectives: Circulating angiogenic factors, e.g. sFlt-1 and PlGF, have a leading role in predicting pre-eclampsia mainly among women at high risk. We aimed to study the predictive value of serial sFlt-1/PlGF measurement in predicting the development of placental syndrome (PS) in women at high risk. Methods: We retrospectively studied data from 78 women with singleton pregnancies at high risk of PS based on previous obstetric or medical history, from the obstetrics and gynecology department, Maastricht UMC (MUMC + ), between January 2015 and February 2017. All women had serial measurement of sFlt-1 using the Kryptor platform (Thermo Fischer). We evaluated the absolute differences in serum concentrations (delta) of sFlt-1, PlGF and sFlt-1/PlGF ratio at different sampling intervals (12-30, 16-30 and 20-30 weeks), as well as the relative change of each factor normalised to its concentration at 12. PS was defined as the development of any of the following: pre-eclampsia, IUGR, HELLP syndrome and placental abruption. Results: Ten out of 78 women developed PS (13%). There were no ...

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