CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 4, May 2013
AFRICA
131
structural and/or functional changes in ventricular function in PE
during late pregnancy and the postpartum period. Our objective
was to characterise the serial changes in the BNP levels in the
third trimester of pregnancy and the early postpartum period.
We performed Doppler studies of the heart and umbilical cord,
measured plasma BNP levels and evaluated obstetric outcomes
in PE and normotensive healthy pregnant patients.
Methods
Primigravidae without any pre-existing history or clinical
evidence of hypertension/cardiac or renal disease were included
in the study after having obtained informed consent. PE was
diagnosed when women in their first pregnancy had a blood
pressure level of at least 140 mmHg systolic and 90 mmHg
diastolic pressure on two occasions over four hours apart for the
first time after the 20th week of pregnancy, associated with at
least one plus of proteinuria on urinary dipstick. For each patient
with PE, at least one healthy normotensive patient was enrolled
in the study. At the time of enrolment the study participants were
not on any medications to lower blood pressure.
A full history and clinical examination was performed.
Systolic and diastolic blood pressures were recorded by
automated readings (Dinamap) after a 30-min period of rest
in the sitting position. Baseline blood investigations included
a full blood count, urea and creatinine, urates and BNP levels.
Obstetric ultrasound examination was performed on all patients.
Foetal wellbeing was assessed sonographically and by Doppler
umbilical flow measurements in relation to appropriate growth
for gestational age, amniotic flow index and placental sufficiency.
Pregnancies were followed and timing and mode of delivery
were noted. Apgar scores and birth weight were recorded and
any admissions to the neonatal intensive care noted. All babies
were asseded at birth and seven days after delivery. A total of 63
normotensive pregnant women with similar age and ethnicity
without a history of cardiovascular disease, pulmonary or
systemic hypertension served as controls.
In this study, blood for BNP estimations from study
participants were obtained at three pre-specified time points,
i.e. at the time of recruitment (28–40 weeks), intra-partum, and
the last specimen was collected between day one and seven
post delivery. The samples were collected in plastic specimen
tubes containing ethylenediamine tetra-acetic acid (EDTA) and
transported on ice to the laboratory where they were centrifuged.
The plasma was stored at −20°C and NT-proBNP was assayed
in batches by standard electrochemiluminescence immunoassay
(ECLIA) using the Modular Analytics E170 (ELECYS module)
and Elecsys 1010/2010 analyzer (Roche diagnostics,). According
to the National Committee for Clinical Laboratory Satndards
(NCCLS), the resting BNP values considered normal for this
methodology lie below 100 pg/ml. The within-assay and total
precision coefficients of variation for NT-proBNP mean 208
pmol/l is 0.8 and 4.5%, respectively. The reading sensitivity is
<
2.0–5 000 pg/ml (0.58–1 445 pmol/l).
Echocardiography and TDI
Shortly after enrolment standard two-dimensional directed
M-mode Doppler echocardiography followed by TDI was
performed with the patient in the left decubitus position. Doppler
echocardiography was performed using a HDE 11 imaging
system (Philips) with a phased-array transducer and an emission
frequency of 3.0 MHz.
The left ventricular (LV) end-systolic and end-diastolic
dimensions, LV wall thickness, and left atrial (LA) dimensions
were measured according to the American Society of
Echocardiography guidelines using the leading edge method.
17
The left atrial volume was estimated using the biplane ellipsoid
formula. The LV end-systolic and end-diastolic volumes and the
ejection fraction were measured from the apical four-chamber
view using the modified Simpson’s method. TDI was performed
with transducer frequencies of 1.8–3.6 MHz with as minimum
optimal gain as possible to obtain the best signal-to-noise ratio.
18
Foetal ultrasound and umbilical artery Doppler
Foetal biometrical ultrasound was performed using a Toshiba
(Nemio) scanner in B-mode and a low-frequency (3.75 MHz)
curvilinear probe.
19
Umbilical artery Doppler studies were then
performed using pulsed-wave Doppler to measure flow velocity
and calculate the resistance index (RI) as follows: peak systolic
velocity was divided by the sum of measurements at peak systole
and diastole [RI
=
systole/(systole
+
diastole)] and averaged over
three cardiac cycles.
Statistical analysis
SPSS version 11.5 (SPSS Inc. Chicago Ill, USA) was used for
statistical analysis. The baseline characteristics were reported as
mean
±
standard deviation and were compared between the two
groups using the Fisher exact test for categorical variables and
the Student’s
t
-test for continuous variables. Outcome measures
were BNP levels, echocardiographic and TDI findings and
obstetric outcomes in both groups.
Chi-square statistics or Fisher’s exact tests were used where
appropriate to examine associations between categorical
exposures and outcomes. Independent two-sample
t
-tests were
used to compare mean BNP levels between two categories.
Results are presented as mean and range in brackets. As BNP
levels were not normally distributed, these are presented as
median values and a Mann-Whitney
U
-test was used to compare
the two groups. Spearman’s test was used for correlation studies.
A
p
-value of
<
0.05 was considered as statistically significant.
Ethics approval was obtained from The University of
KwaZulu-Natal Biomedical Research Ethics Committee.
Results
One hundred and fifteen primiparous patients (63 normotensive
and 52 pre-eclamptics) were recruited (Table 1). A total of
113 participants had complete longitudinal BNP values for all
three pre-specified time periods. There was no difference in
gestational age at entry and in mode of delivery in both groups.
The mean age of the pre-eclamptics was slightly higher (21.5
±
4.7 vs 20.4
±
3.7 years) but this difference was not significant
(
p
<
0.06). The body mass index in the pre-eclamptic group was
significantly higher compared to the normotensive pregnancies
(29.4
±
7.9 vs 27.9
±
5.5;
p
<
0.05). There were 17 patients in
each group who were HIV infected, five of whom in each group
had CD
4
cell counts
<
200 cells/mm.
Most patients were managed with the following
antihypertensive agents: methyldopa or nifedipine XL orally.
