CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 4, May 2013
AFRICA
133
(2.6
±
0.8 vs 3.14
±
0.42 kg;
p
<
0.0001). One neonate in the
pre-eclamptic group was born with Down syndrome.
There were two neonatal deaths. Patient 1, a 25-year-old
P0G1, who was HIV infected presented at 28 weeks of gestation
in pulmonary oedema. The blood pressure value was 224/134
mmHg, pulse rate was 106 beats per minute, proteinuria 2
+
and oedema 1
+
. Her tissue Doppler E/E
a
ratio was 42, RI was
0.74, uric acid level was 0.43 mmol/l and platelet count was
122
×
10
9
/l. Rapid-acting blood pressure-lowering drugs (adalat,
hydrallazine, labetalol, aldomet and MgSO
4
) were administerd
and she was induced at 30 weeks. She delivered a 1-kg baby with
poor Apgar scores who died an hour later.
The second patient, a 24-year-old P0G1 who was HIV
uninfected presented at 40 weeks of gestation with a BP of
126/82 mmHg. Her tissue Doppler E/E
a
was 15.4, RI was
0.67, and ejection fraction was 68%. She delivered vaginally a
3.4-kg baby with low APGAR scores who died two days later in
respiratory distress.
Discussion
This was the first study to evaluate haemodynamic alterations
in pre-eclampsia using simultaneous BNP and tissue Doppler
markers of the left ventricular filling pressure (Fig. 2). The
findings indicate that despite the contracted blood volumes in
PE, the haemodynamic changes that accompany vasoconstriction
in PE are associated with significant changes in LV filling, as
reflected by the TDI and BNP levels. The study confirms that the
intense vasoconstriction in PE is accompanied by increased left
ventricular afterload, accompanied by a reduced cardiac output,
hypovolaemia and increased cardiac filling pressures.
Recent studies have confirmed that BNP concentrations are
elevated in PE and other hypertensive disorders of pregnancy.
19-22
The increased serum BNP levels in PE are greater than
that documented in normotensive pregnancies,
23,24
suggesting
that BNP activation in PE is a response to changes in the
maternal circulation that reflect the pathophysiological changes
in the utero–placental unit. It is known that median BNP
levels are low (
<
20 pg/ml) and remain stable throughout
gestation in normotensive pregnancies.
24
BNP levels rise in
pregnancies complicated by mild PE and are even higher in
severe pre-eclamptics, probably reflecting ventricular strain and/
or sub-clinical cardiac dysfunction secondary to the increased
afterload that is characteristic of PE.
13,24
Itoh
et
al
.
13
reviewed the charts of 15 obstetric patients who
presented with acute dyspnoea, and found that seven had PE,
with elevated BNP levels. This correlated with acute ventricular
overload and they responded well to volume management and
diuresis. In two patients, markedly elevated serum BNP levels
and significant left ventricular dysfunction was found, which was
not apparent by standard clinical evaluation.
13
In patients with
severe pregnancy-induced hypertension, an eight-fold increase
in BNP levels has been documented, with a positive correlation
between the plasma BNP levels and the mean arterial blood
pressure (
r
=
0.62,
p
<
0.001).
18
Until recently, very little was known about BNP levels
during pregnancy. Hameed
et
al.
25
have shown that although
pregnant BNP levels are approximately two-fold higher than their
non-pregnant counterparts, they do not significantly fluctuate
and probably reflect the physiological increase in cardiac
output during pregnancy. Our study also confirms that BNP
levels remain normal in the peripartum period in normotensive
pregnant women.
Circulating plasma BNP levels are mildly elevated in healthy
pregnancies compared to non-pregnant controls. A longitudinal
study of 29 healthy pregnant women in each trimester and in
the postpartum period has shown no significant differences
in the median BNP levels in the various stages of pregnancy
and postpartum [first trimester 20 (10–115) pg/ml]. Although
pregnant BNP levels were twice as high as the non-pregnant BNP
levels, there were no significant differences among the cases
compared to non-pregnant controls. These authors concluded
that pregnancy is associated with a small increase in the BNP
levels compared with non-pregnant women.
25
By contrast, women with PE show adaptations to the increase
in systemic blood pressure with significant modification of left
ventricular structure and function.
26
Echocardiographic studies
show statistically significant increases in LV mass, increased
LV end-systolic and end-diastolic volumes, accompanied by
significant reductions in LV ejection fraction and percentage of
fractional shortening.
27-29
We also found an increase in the size of the left atrium in the
pre-eclamptic group and although not statistically significant,
this probably reflects early cardiac structural changes in PE.
More importantly, we showed elevated tissue Doppler E/E
a
ratios
in the pre-eclamptic patients compared to the normotensive
group of patients (11.02
±
5.6 vs 9.16
±
2.6,
p
<
0.05). This
increase was attributed to a rise in the tissue Doppler E wave and
probably reflects rising cardiac filling pressures in PE.
All other differences in the echocardiographic parameters
were statistically insignificant, pointing to the sensitivity of tissue
Doppler in detecting early changes in diastolic filling pressures.
Although tissue Doppler-derived E
a
correlates with the ventricular
time constant and is a relatively load-independent measure of
myocardial relaxation in patients with cardiac disease, in our
study it did not appear as sensitive as BNP, which is emerging
as a new marker in identifying early haemodynamic changes. In
patients with PE, BNP has been observed to be linearly related to
the left ventricular structural and functional changes observed.
16
In this study we have shown that plasma BNP levels
were significantly increased in pre-eclamptic compared to
normotensive patients in the antepartum period, and decreased
significantly in the postpartum period. Women with PE have
increased sensitivity to angiotensin II, resulting in increased
TABLE 4. MATERNALAND FOETAL OUTCOME
Parameter
Normotensive
pregnancies
(
n
=
62)
Pre-eclamptic
(
n
=
48)
Thrombocytopaenia
Pulmonary oedema
Eclampsia
HELLP syndrome
1
0
0
0
10
2
11
1
Birth weight mean
±
SD (kg)
Apgar scores
1 min
5 min
2.64
±
0.8
7 (0–0)
8 (0–0)
3.14
±
0.42
8 (3–0)
9 (0–)
Perinatal outcome
63
52
Live births
56
49
Still births
0
2
Early neonatal death
1
1
Thrombocytopaenia
= <
150
×
10
9
/l.
