insufficiency, or gastrointestinal perforation, and were thought to
be related to the severity of maternal disease and not necessarily
related to labetalol use [26]. No significant differences were found in
occurrence of bradycardia and hypoglycemia between treatment and
control groups [26]. No significant differences in rates of bradycardia,
hypotension and hypoglycemia were found when intravenous and
oral labetalol were compared [26]. The authors hypothesized that
hypoglycemia may be more due to prematurity than to drug therapy,
as hypoglycemia affected over 40% of infants in both the labetalol and
control groups [26]. Additionally, the authors observed the adverse
effects of maternal labetalol on neonates may be less severe than
previously thought, and this topic warrants further study [26].
Furthermore, a retrospective chart review compared labetalol or
nifedipine in women with a diagnosis of gestational hypertension,
mild preeclampsia, severe preeclampsia, and HELLP syndrome. They
were grouped according to diagnosis and the safety and efficacy of
the two agents were compared [13]. In the severe preeclampsia and
HELLP syndrome group, there were no significant differences found
in rates of maternal blood pressure control, rates of cesarean section,
intrauterine growth restriction, gestational age at delivery, birth
weight, and Neonatal Intensive Care Unit (NICU) admissions [13].
However, significant differences were found within the gestational
hypertension/preeclampsia group [13]. The labetalol group showed
a 38.8% incidence of intrauterine growth restriction compared
to 15.5% in the nifedipine group, and the labetalol group also
demonstrated higher rates of fetal worsening as demonstrated by
fetal heart monitoring (33.3% versus 14.2%) [13]. The study found
no significant differences in rates of adverse effects, with headache
and nausea being the most frequently observed adverse effects of both
medications [13].
Labetalol was compared to methyldopa for use in pregnancyinduced
hypertension in a prospective randomized trial completed
by Molvi, et al [20]. One hundred fifty women were randomized
to receive labetalol plus standard care, methyldopa plus standard
care, or the control group of standard care alone [20]. The primary
outcome was any maternal or fetal adverse events, including maternal
death, preeclampsia, eclampsia, cesarean section, fetal death, neonatal
death within first week, preterm birth, low Apgar score of less than
5 at five minutes, and neonatal intensive care unit admissions [20].
Occurrence of severe hypertension and proteinuria were significantly
reduced in both treatment groups compared to the control group
[20]. Severe hypertension occurred in 16.3% of the women treated
with methyldopa, while only 4% of the labetalol treatment progressed
to severe hypertension [20]. There were also significantly fewer
preterm births and small for gestational age babies in the treatment
groups, and the authors concluded that antihypertensive therapy
was beneficial in preventing morbidity associated with pregnancyinduced
hypertension [20].
Methyldopa
Methyldopa, or α-methyldopa, is an alpha2 adrenergic agonist
which causes a reduction in blood pressure by decreasing the effects
of the sympathetic nervous system [27]. Methyldopa is frequently
used to treat hypertension during pregnancy [5]. This medication
may be administered by either intravenous or oral routes [27].
Methyldopa has the most long-term safety data to support
its use during pregnancy [28]. No adverse effects on growth and
development were seen in a 7.5 year follow-up in children exposed
to methyldopa in utero [28]. The effects of methyldopa on placental
perfusion were studied using the results of uterine artery Doppler
scans at baseline, after 24 hours, and after 48 hours of initiation of
medication therapy [29]. Methyldopa significantly reduced blood
pressure when compared to a control group, and did not exert any
significant changes on uterine artery Doppler measurements from
baseline to 24 hours and 48 hours after medication initiation [29].
When compared to patients treated with labetalol, women given
methyldopa had a higher incidence of severe hypertension and higher
rates of antenatal hospitalizations [20]. The infants of women treated
with methyldopa were admitted to the neonatal intensive care unit
more often than those exposed to labetalol (22.4% versus 8%) [20].
Nicardipine/nifedipine
Calcium channel blockers inhibit the L-type calcium channels in
the cardiac and vascular smooth muscle cells, which exerts negative
inotropic effects on the heart and causes vasodilation, leading
to decreased systemic vascular resistance [18]. Both nicardipine
and nifedipine have been studied for use during pregnancy [1,5].
Nicardipine has been found to be highly selective for vascular smooth
muscle compared to cardiac muscle [18]. Nicardipine has also been
found to have more selective effects than nifedipine, resulting in less
reflex tachycardia