Predicting delivery of a small‐for‐gestational‐age infant and adverse perinatal outcome in women with suspected pre‐eclampsia

Abstract

ObjectiveTo evaluate the test performance of 47 biomarkers and ultrasound parameters for the prediction of delivery of a small‐for‐gestational‐age (SGA) infant and adverse perinatal outcome in women presenting with suspected pre‐eclampsia.MethodsThis was a prospective, multicenter observational study in which 47 biomarkers and ultrasound parameters were measured in 397 women with a singleton pregnancy presenting with suspected preterm pre‐eclampsia between 20 + 0 and 36 + 6 weeks' gestation, with the objective of evaluating them as predictors of subsequent delivery of a SGA infant and adverse perinatal outcome. Women with confirmed pre‐eclampsia at enrollment were excluded. Factor analysis and stepwise logistic regression were performed in two prespecified groups stratified according to gestational age at enrollment. The primary outcome was delivery of a SGA infant with a birth weight < 3rd customized centile (SGA‐3), and secondary outcomes were a SGA infant with a birth weight < 10th customized centile and adverse perinatal outcome.ResultsIn 274 women presenting at 20 + 0 to 34 + 6 weeks' gestation, 96 (35%) delivered a SGA‐3 infant. For prediction of SGA‐3, low maternal placental growth factor (PlGF) concentration had a sensitivity of 93% (95% CI, 84–98%) and negative predictive value (NPV) of 90% (95% CI, 76–97%) compared with a sensitivity of 71% (95% CI, 58–82%) and a NPV of 79% (95% CI, 68–87%) for ultrasound parameters (estimated fetal weight or abdominal circumference < 10th centile). No individual biomarker evaluated had a better performance than did PlGF, and marker combinations made only small improvements to the test performance. Similar results were found in 123 women presenting between 35 + 0 and 36 + 6 weeks' gestation.ConclusionIn women presenting with suspected preterm pre‐eclampsia, measurement of PlGF offers a useful adjunct for identifying those at high risk of delivering a SGA infant, allowing appropriate surveillance and timely intervention. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

A clinical evaluation of placental growth factor in routine practice in high-risk women presenting with suspected pre-eclampsia and/or fetal growth restriction

“…Our results support this recommendation for placental dysfunction with a maternal component, as we had no diagnoses of PE within 7 days of a normal PlGF result. In this high-risk cohort angiogenic marker testing also assisted in the management of suspected SGA with a detection rate of 80% within a week, however two cases of severe FGR were not identified by an abnormal PlGF result (test-birth interval 5 days) highlighting the heterogeneous aetiology of this condition and the ongoing need for further research regarding the relationship between placental dysfunction and maternal angiogenic marker levels (13).…”

“…Preclinical (7), in vitro (8) and ex vivo studies (9) have all demonstrated a reduction in PlGF and/or an elevation of sFlt in the context of PE and placental dysfunction. Previous clinical studies have also demonstrated that there is a significant change in circulating angiogenic markers in women who develop PE and those with related placental dysfunction (10)(11)(12)(13). The NICE Diagnostics Assessment Panel (14) recently reviewed the published literature related to the clinical utility of angiogenic marker testing in suspected PE and concluded that a negative test could be used to safely rule out disease for the next 7-14 days(REF).…”

A placenta clinic approach to the diagnosis and management of fetal growth restriction

“…84 In a prospective cohort of 274 women with suspected preeclampsia presenting at 20-34 weeks' gestation, low circulating PlGF (<100 pg/mL) had high sensitivity to detect SGA births (n ¼ 96) below third customized birthweight centile (sensitivity 93%, negative predictive value [NPV] 90%), which was superior to fetal weight estimation by ultrasound (sensitivity 71%, NPV 79%). 85 An earlier multicenter study by the same group, of 592 women with reduced symphysisfundal height measurements, found that combining PlGF with ultrasound biometry increased the sensitivity from 58-69% for the detection of customized growth at the third centile (with the same 93% NPV). 86 As an adjunct to multiparameter screening for placental dysfunction in the second trimester, PlGF offers only modest gains and is therefore not recommended in low-risk pregnancies.…”

“…This phenomenon develops during second trimester, confounding utility of placental volume as component of screening for fetal growth restriction. See Supplementary Videos 10 and 11. severe early-onset disease associated with hypertension and abnormal umbilical artery Doppler, and now including women identified with very low PlGF (<12 pg/mL) 71,85 or abnormal sFlt-1/PlGF ratios. 69,88 Corticosteroids pose a specific challenge in the context of severe FGR with abnormal umbilical artery and fetal Doppler waveforms.…”

The ability of late pregnancy maternal tests to predict adverse pregnancy outcomes associated with placental dysfunction (specifically fetal growth restriction and pre-eclampsia): a protocol for a systematic review and meta-analysis of prognostic accuracy studies

“…Sampling later in pregnancy could provide greater predictive accuracy, as this is closer to disease onset (compared to first or second trimester sampling). This is supported by studies evaluating biomarkers associated with placental function in the third trimester [16][17][18][19]. There is most evidence to support the use of late pregnancy maternal tests for the prediction of pre-eclampsia, e.g., tests based upon placental growth factor (PlGF), but other studies also report benefits in high-risk and unselected populations for the prediction of delivering a SGA infant [18,20].…”