Cardiovascular Journal of Africa: Vol 29 No 5 (September/October 2018)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 5, September/October 2018

AFRICA

315

categorised according to their CPR percentile for gestational age

and we assessed the accuracy of a CPR value less than the fifth

percentile in predicting adverse outcome. Of the 54 cases with

CPR values, 33 (61%) had values less than the fifth percentile.

The sensitivity of CPR

p5 in predicting an adverse event

was 67% and the specificity was estimated at 43%, which cannot

be regarded as a good predictor for adverse outcome. The

possible explanation for this is that an abnormal CPR probably

reflects an established hypoxaemic state and is probably not a

predictive parameter, as we were trying to establish in this study.

The patients we investigated were stable/mild placental-mediated

conditions, i.e. uncompensated IUGR (non-hypoxaemic,

non-acidotic) and well-controlled pre-eclamptics (stable control

on a single agent).

The clinical phenotypes of IUGR and PE depend on the

degree of placental maladaptation and degree of lack of vascular

remodelling. Both conditions can be grouped as ischaemic

placental disease or placental-mediated disease. In EO-PE there

is down-regulation of the interstitial trophoblastic invasion, while

endovascular trophoblastic invasion is limited to the decidua.

The combined IUGR and PE clinical phenotypes are the

result of a more advanced degree of placental maladaptation,

and the high number of adverse outcomes in the PE–IUGR

group is consistent with this pathophysiology. This is therefore

a dynamic process and, depending on the clinical phenotype

and placental lesion, will in worse outcomes, result in hypoxia,

oligohydramnios (due to decreased foetal perfusion), maternal

multi-systemic organ affectation (such as HELLP or eclampsia),

foetal acidosis and death.

From whatever clinical phenotype is realised, the path to

deterioration can be foetal and/or maternal, depending on

levels of placental ischaemia and the associated production of

increased levels of toxic factors such as sFLt-1 and endoglin.

Present standard monitoring models, done in the early third

trimester, may not be predictive of later adverse outcomes. For

example, UA RI becomes abnormal only if more than 30 to

40% of the placenta is non-functional,

28,29

MCA RI becomes

abnormal only at the onset of hypoxia,

and DV changes are late

changes in the cascade of cardiovascular deterioration, already

reflecting acidosis and myocardial necrosis.

Furthermore, the

vast majority (

72%) of ‘unexplained’ stillbirths at term are

so-called appropriate for gestational age, that is between p10 and

p50, so biometry is also not entirely helpful.

As early hypoxia and increasing afterload both impact on

cardiac function, the MPI is well placed to become a predictor

of adverse obstetric outcome, as demonstrated in this study. The

use of MPI together with biochemical markers, such as sFlt-1

and PLGF,

may further improve its sensitivity. This project

is a continuation of our group’s quest to further define the

clinical use of MPI in high-risk obstetric conditions and find its

appropriate place in antenatal foetal surveillance, in the context

of present standard foetal monitoring models.

The main limitation of the study is the limited numbers

in the groups under investigation, but the results nonetheless

highlight the great potential of cardiac Doppler as an important

adjunct to standard monitoring models in placental-mediated

disease. It makes the case to further corroborate these findings

in larger trials and to fine-tune the place and implementation

of cardiac Doppler in mainstream monitoring of cases with

placental-mediated disease. Another limitation is that it requires

training and experience to obtain a reliable MPI result and

it can be confounded by user bias. However this parameter

shows good reproducibility when the valve-click method of

establishing landmarks is used, as we have demonstrated in our

study, establishing reference intervals of the MPI in normal

pregnancies.

Conclusion

A single elevated value of the MPI (

-score

4.5) in the

third trimester in stable placental-mediated disease is a strong

indicator of adverse obstetric outcome later in pregnancy.

This has the potential to be incorporated, in conjunction

with standard monitoring models, in stable placental-mediated

disease to predict an adverse event later in pregnancy and thus

to reduce perinatal morbidity and mortality.

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