Among pregnancies with clinical risk factors for pre-eclampsia or fetal growth restriction, PlGF in mid-pregnancy is unhelpful in identifying women and babies at particular risk of complications.
A new study, funded by the Fetal Medicine Foundation and led by Professor Laura Magee, has found that among pregnancies with clinical risk factors for pre-eclampsia or fetal growth restriction, measuring serum placental growth factor (PlGF) at the time of the routine 20-week fetal ultrasound scan is not helpful to inform clinical care pathways.
Pre-eclampsia and fetal growth restriction are leading causes of maternal and fetal/newborn mortality and morbidity, here in the UK and worldwide. Identifying these pregnancies is a key objective of antenatal care, and national guidance advises that maternity care-providers identify women with clinical risk factors, so that they can be offered enhanced surveillance and/or low-dose aspirin. However, it is recognised that clinical risk factors are common, and they pick up less than half of pregnancies that end in complications, including gestational hypertension, stillbirth, and prolonged neonatal intensive care unit admission.
As low serum placental growth factor (PlGF) has been associated with both pre-eclampsia and fetal growth restriction, this study evaluated whether PlGF could be measured at 19-23 weeks' gestation, in conjunction with the routine ultrasound assessment for fetal anomalies, as a 'contingency screening tool' to improve the predictive performance of clinical risk factors for the subsequent development of pre-eclampsia, fetal growth restriction, or other related complications.
Over 30,000 pregnancies at 19-23 weeks' gestation were screened with PIGF at King's College Hospital and Medway Maritime Hospital. From that dataset, 33% of pregnancies had a clinical risk factor for pre-eclampsia or fetal growth restriction, and they experienced 42-55% of the adverse outcomes during or after pregnancy. When PlGF testing at 19-23 weeks' gestation was added in a second step to earlier risk factor screening, a low PlGF was associated with a higher risk of problems before term gestational age, but these represented
Complications at term gestational age could not be identified with accuracy, by clinical risk factor screening in early pregnancy, PlGF alone at 19-23 weeks' gestation, or such PlGF testing following earlier clinical risk factor screening. Early pregnancy risk factor screening must not be used to guide timed birth at term.
Professor Laura Magee
Considering this, the authors argue that clinical risk factor screening for pre-eclampsia or fetal growth restriction results in a high screen-positive rate, but a poor detection rate of adverse outcomes, and the high false-positive rate cannot be reduced by PlGF testing at 19-23 weeks of gestation.
The risk of pre-eclampsia or fetal growth restriction is best identified by the Fetal Medicine Foundation competing risks model, which includes but is not limited to PlGF testing in early pregnancy. Future research must address whether repeat testing of PlGF later in pregnancy has a role to play in further refining the risk of adverse pregnancy outcomes.
Professor Kypros Nicolaides
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Professor of Women's Health
Professor of Fetal Medicine
