o_1977r8vv9vk1ts2ms0kd8pksa.pdf

302 H. Odendaal
Time to Establish the Ground Values
In an excellent opinion article, Lees [58] expressed
his disappointment about the systemic review by
Chien et al. [19] and referred to recent findings that
would help one to interpret results more uniformly.
He stressed the optimal screening time of 20±24
weeks and the acceptance of bilateral notching above
unilateral notching. A high mean uterine artery pulsatility
index was more reproducible and objective
basis for screening than bilateral notches alone. He
expressed the hope that these recommendations will
be accepted for standardized large multicentre studies
to elucidate some of the existing uncertainties.
Other Predictions
Although this article concentrates on the prediction of
hypertension and pre-eclampsia, other clinically important
outcomes were also determined; however, the
overview by Chien et al. [19] demonstrated that the
prediction of intrauterine growth restriction and intrauterine
death was poor. Uterine artery Doppler velocimetry
has also been studied in women with antiphospholipid
syndrome [32, 102]. They found it to be useful
in predicting pre-eclampsia and SGA infants. Outcome
of pregnancy in women with normal uterine artery
Doppler flow velocity waveforms was good.
Aspirin
The well-known CLASP study showed a disappointing
effect of aspirin on the prevention of pre-eclampsia,
demonstrating only a 12% reduction in its incidence,
which was not significant. No significant effect on the
incidence of IUGR or perinatal deaths was detected;
however, a 22% reduction (9.9% CI, 40% reduction to
3% increase; p=0.02) was found in women where the
prophylaxis started at 20 weeks or earlier [20]. A later
meta-analysis for the Cochrane library [55] addressed
42 trials in more than 32,000 women. A 15% reduction
in the risk of pre-eclampsia was associated with
the use of antiplatelet agents (RR 0.85, 95% CI 0.78±
0.92). The number needed to treat was 89. The reduction
in the risks of pre-eclampsia was statistically significant
for women randomized before 20 weeks' gestation
(RR 0.86, 95% CI 0.77±0.97) but borderline for
those entered after 20 weeks. Not all studies found aspirin
to be protective. For example, a large study, in
2539 women at high risk, enrolled between 13 and 26
weeks, failed to demonstrate any beneficial effect of
low-dose aspirin on the incidence of pre-eclampsia
[17, 18]. Predictors of pre-eclampsia in women at
high risk were nulliparity and a mean arterial pressure
> 85 mmHg at enrolment [17, 18].
Following the success of aspirin prophylaxis in
early pregnancy in the CLASP and other small studies,
several randomized controlled trials were done in
women with abnormal uterine artery Doppler flow
velocity waveforms.
Vainio et al. [99] randomized 90 women with bilateral
notches to receive either a placebo or 0.5 mg/kg
per day acetylsalicylic acid; the latter was associated
with significant reduction in the incidence of pregnancy-induced
hypertension (11.6% vs 37.2%; RR
0.31; 95% CI 0.13±0.78). The incidence of pre-eclampsia
was also reduced (4.7% vs 23.3%; RR 0.2; 95% CI
0.05±0.86).
Harrington et al. [45] randomized 2116 women for
abnormal uterine artery Doppler flow velocity waveforms
(bilateral notches with a mean RI > 0.55, unilateral
notch with a mean RI > 0.65 or with a mean RI
> 0.70 in the absence of notches) to receive a placebo
or 100 mg slow-release aspirin daily from 17±23 weeks'
gestation. Although the incidence of pre-eclampsia was
not reduced, there was an improvement in outcome by
reducing complications associated with uteroplacental
insufficiency. Goffinet et al. [37] randomized 3317
low-risk women from 18 centers into a Doppler group
or a control group. An abnormal Doppler result was defined
as diastole :systole > 35% or a notch on at least
one of the uterine arteries. These patients received
100 mg aspirin daily until they reached a gestational
age of 35 weeks. There was no effect on the incidence
of pre-eclampsia (RR 1.99; 95% CI 0.97±4.09). Bar et
al. [9] found no effect of 60 mg aspirin on fetal circulation
parameters in their 87 women who were recruited
for the CLASP study. In a similar study, Grabet al. [39]
found no effect of 100 mg aspirin per day on the uteroplacental
or fetoplacental hemodynamics. It also did
not cause moderate or severe constriction of the ductus
arteriosus.
As the mentioned results were conflicting, Coomarasamy
et al. [22] did a meta-analysis of five trials
which assessed the effect of low-dose aspirin on the
incidence of pre-eclampsia in women with abnormal
uterine Doppler. Five relevant trials were found. Pooling
their results demonstrated a significant reduction
in pre-eclampsia (OR 0.55; 95% CI 0.32±0.95). The
baseline risk of pre-eclampsia in these women with
abnormal uterine artery Doppler flow velocity waveforms
was 16%. The number of women to be treated
to prevent one case of pre-eclampsia was 16. Babies
of mothers who received aspirin were on average 82 g
heavier.
Summary
When one tries to answer the initial questions, there
are still many uncertainties; these relate more to the
method and timing of the screening (Table 19.1) than
to the prevention of complications with early administration
of low dose aspirin: