The Future of PlGF
The National Institute for Health and Care Excellence recommends a
single Triage PlGF test or Elecsys sFlt-1/PlGF ratio as a rule-out test,
concluding that the evidence is currently insufficient to recommend use
as a rule in test.13 Furthermore, the guidance is
clear that testing should be used to aid diagnosis of pre-eclampsia, and
not a wider syndrome of placental disease.
The role of repeat PlGF sampling has not been fully investigated and the
impact of repeat testing on maternal and perinatal outcomes is unknown.
This is particularly important in women in whom a clear risk trajectory
or diagnosis is not reached at initial presentation, but ongoing
suspicion of disease remains. One study has recently suggested that
repeat PlGF testing retains high diagnostic accuracy, with a high
sensitivity and NPV.29 Another study demonstrated
increasing sFlt-1/PlGF ratios in women who went on to develop
pre-eclampsia or adverse perinatal outcomes.30However, before repeat testing is recommended, clinical and
cost-effectiveness need to be established, given as an explicit research
recommendation in the diagnostic guideline.13 This is
being addressed by the PARROT-2 trial, a multicentre randomised
controlled trial of repeat revealed PlGF-based testing compared to usual
care with repeat concealed testing (ISRCTN85912420).
The role of PlGF in the assessment of pre-eclampsia in multi-fetal
pregnancy is uncertain, as normal ranges and interpretation have not
been defined. There are a few small studies to date, with conflicting
results.31-33 The largest of these studied 79 women,
presenting with suspected pre-eclampsia and found elevated sFlt-1/PlGF
ratio was associated with adverse outcomes.31 Although
a smaller population of women, use of PlGF-based testing remains an
important challenge due to the higher prevalence of pre-eclampsia in
multi-fetal pregnancy.
PlGF-based testing in the assessment of early-onset fetal growth
restriction warrants further study and there is conflicting evidence.
One study of 213 pregnancies showed that low PlGF had a sensitivity of
98.2% with a NPV of 99.2% for placental fetal growth restriction
(confirmed on placental histology).34 A large
prospective cohort study of 4,512 women found that addition of the
sFlt-1/PlGF ratio to ultrasonic assessment improved the positive
likelihood ratio for delivering a small-for-gestational-age
infant.35 Another study demonstrated that PlGF
outperformed both ultrasound and numerous other
biomarkers.36 However, a multicentre study including
592 women demonstrated that PlGF performed no better than estimated
fetal weight <5th centile in predicting
delivery of a small-for-gestational-age infant.37
Other outstanding issues include the ability of PlGF-based tests to risk
stratify in established disease, as well as the role of PlGF in
low-resource countries. By far the greatest burden of morbidity and
mortality due to pre-eclampsia is borne by women and their infants in
low and middle-income settings. Initial evidence of the impact of
PlGF-based testing in this setting is promising.38, 39
Finally, now that value in diagnosis of pre-eclampsia has been proven,
PlGF and sFlt-1 may prove informative to guide treatments that influence
the outcome or ameliorate development of the
disease.40