[Downloaded free from http://www.clinicaltdd.com on Sunday, October 7, 2018, IP: 181.113.175.

10]

REVIEW

Medication for management of pregnancy-induced

hypertension
Yi Lin, Ying Zhang, Yi-Nong Jiang, Wei Song*
Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China

*Correspondence to: Wei Song, Ph.D., songwei8124@163.com.

orcid: 0000-0002-4973-7236 (Wei Song)

Abstract
Hypertension refers to increased arterial blood pressure and can be divided into two categories: primary and secondary. Primary hypertension
caused by angiogenic degenerative changes is a degenerative disease. With liberalization of China’s reproduction policy and increases
in maternal age, the prevalence of pregnancy-induced hypertension (PIH) in China has increased gradually. PIH is not a type of primary
hypertension, but there are differences in the treatment of these two types of hypertension. Here, we review the choice and use of drugs for
PIH management using drugs for the management of primary hypertension as a reference. First-line drugs such as labetalol, nifedipine, or
methyldopa should be taken via the oral route if blood pressure is ≥ 150/90 mmHg. For chronic hypertension, other drugs should be added
after the first drug at the highest concentration has been revealed to be ineffective. If the blood pressure of patients with acute hypertension is
≥ 160/110 mmHg, maternal stroke or eclampsia can result. If PIH patients are about to deliver, they can be given labetalol (i.v.), hydralazine
(i.v.) or nifedipine (p.o.). Moreover, all anti-hypertensive treatments should be based on considerations of maternal and fetal safety.

Key words: pregnancy; hypertension; preeclampsia; eclampsia; medication

doi: 10.4103/2542-3975.235153
How to cite this article: Lin Y, Zhang Y, Jiang YN, Song W. Medication for management of pregnancy-induced hypertension. Clin Trials
Degener Dis. 2018;3(2):83-87.

INTRODUCTION thrombocytopenia (platelet count < 100 000/mL), impaired

Hypertension refers to increased arterial blood pressure.
Long-term hypertension can lead to coronary artery disease,
stroke, heart failure, atrial fibrillation, peripheral vascular
disease, vision loss, chronic kidney disease, and dementia.1,2
Hypertension can be divided into primary and secondary
types. 3 Primary hypertension accounts for 90–95% of
hypertension cases. 3,4 Primary hypertension caused by
angiogenic degenerative changes is a type of degenerative
disease.5
Blood pressure (BP) measured at intervals during pregnancy
> 140/90 mmHg is considered to denote PIH. The prevalence
of PIH worldwide is 8–10%,6,7 whereas that in China is
5.6–9.4%.8 China has a two-child policy, so the maternal age
may increase, which may further increase PIH prevalence.
Drugs used for the management of primary hypertension
are ganglionic blockers, adrenergic neuron-blocking agents,
alpha-blockers, diuretics, and beta blockers.9 PIH is different
from primary hypertension, but similarities exist in the
treatment of these two types of hypertension. Using drugs for
the management of primary hypertension as a reference, we
review the selection and use of drugs for PIH management to
provide evidence for its clinical treatment.
CLASSIFICATION AND DEFINITION OF PIH
According to the guideline set by the American Congress of
Obstetricians and Gynecologists (ACOG) in 2013, there are
four categories of hypertension during pregnancy.
The first type of hypertension during pregnancy is
preeclampsia-eclampsia. In the absence of proteinuria,
preeclampsia is diagnosed as hypertension in association with
liver function (increased blood levels of liver transaminases
to twice the normal concentration), new development of
renal insufficiency (increased serum creatinine > 1.1 mg/dL
or doubling of serum creatinine in the absence of other renal
disease), pulmonary edema, or new-onset cerebral/visual
disturbances. The second type is chronic hypertension. This
is defined as systolic blood pressure (SBP) > 140 mmHg
and/or diastolic blood pressure (DBP) ≥ 90 mmHg before
pregnancy or at a gestational age of 20 weeks, or if BP at 12
weeks post partum remains abnormal. The third type is chronic
hypertension with superim-posed preeclampsia. This is chronic
hypertension in association with preeclampsia. The final type
is PIH developing after 20 weeks without proteinuria or the
systemic findings mentioned above.10,11 For the convenience of
initiating antihypertensive medication, PIH severity is usually
divided into two categories: (i) mild–moderate (SBP: 140-159
mmHg; DBP: 90–109 mmHg) and severe (SBP ≥ 160 mmHg;
DBP ≥ 110 mmHg).12
PATHOPHYSIOLOGIC CHANGES IN PIH
Under physiologic conditions, the BP of pregnant women
begins to decrease after pregnancy onset. Simultaneously,
cardiac output increases slightly, and peripheral vascular
resistance decreases significantly. Moreover, renal blood flow
and the estimated glomerular filtration rate increase. These
conditions peak at 12 weeks of gestational age. Peripheral
vascular resistance and BP also increase slightly during
pregnancy. These tendencies return to the pre-pregnancy level
after 36 weeks of gestational age.13 The pathologic changes
of PIH are spasm of small arteries and sodium retention in

© 2018 Clinical Trials in Degenerative Diseases | Published by Wolters Kluwer - Medknow 83

[Downloaded free from http://www.clinicaltdd.com on Sunday, October 7, 2018, IP: 181.113.175.10]
Lin et al. / Clin Trials Degener Dis
Table 1: Oral medication and doses used in pregnancy-induced hypertension
Drug Dose
Methyldopa* 0.5–3 g/d, 2–4 times
Labetalol# 200–1200 mg/d, 2–3 times
Nifedipine# 30–90 mg/d of a slow-release
preparation, 1–3 times
Hydralazine# 50-300 mg/d, 2–4 times
β-Receptor blockers# Depends on specific agent
Hydrochlorothiazide# 25 mg/d
Angiotensin-converting enzyme
(ACE) inhibitors and angiotensin
(AT1) receptor antagonists†
Note: *Drug therapy is indicated for uncomplicated chronic hypertension if the diastolic blood pressure ≥ 100 mmHg (using the Korotkoff V phase sounds for measurement
of diastolic blood pressure). Treatment at lower levels may be indicated for patients with diabetes mellitus, renal disease, or target-organ damage. #Drugs meet the
United States Food and Drug Administration classification. †Some agents have been omitted (e.g., clonidine, alpha-blockers) as a result of limited data on use for chronic
hypertension in pregnancy.
the whole body, which can result in target-organ damage and
eclampsia. In addition to pathologic changes, several risk
factors can induce eclampsia: nulliparity; multiple gestation;
family history of preeclampsia; chronic hypertension; diabetes
mellitus; renal disease; history of preeclampsia, especially if
early (before 34 weeks) in a previous pregnancy; history of
hemolysis; increased level of liver enzymes; HELLP syndrome
in a previous pregnancy, obesity; hydatidiform mole.
DAMAGE CAUSED BY PIH
PIH is a pregnancy complication that threatens maternal and
fetal health. The risk of restriction of fetal growth and placental
abruption is increased greatly in PIH patients.14 In the mother,
the risk of brain edema, acute heart failure, stroke, and acute
renal failure is also increased due to the pathologic changes
wrought by PIH. A recent large meta-analysis showed that
women with a history of pre-eclampsia had approximately
double the risk of ischemic heart disease, stroke and venous
thrombo-embolic events 5–15 years after the pregnancy.15
Also, the risk of developing hypertension is almost four-fold
in women with a history of pre-eclampsia.16
NON-PHARMACOLOGIC MANAGEMENT OF PIH
In women with PIH, a normal diet without salt restriction is
advised, particularly close to delivery. Salt restriction may
lead to small intravascular volume. Calcium supplementation
(≥ 1 g/day) is associated with a significant reduction in pre-
eclampsia risk, particularly for women on low-calcium diets.
Fish-oil supplementation and supplementation with vitamins
and nutrients have no role in the prevention of hypertensive
disorders.17 Clinical trials have not shown a beneficial effect
of vitamin D supplementation on preeclampsia prevention, but
the dose, timing, and duration of supplementation should be
investigated in future research.18 Aerobic exercise for 30–60
minutes twice a week during pregnancy can reduce PIH risk
significantly.19
84
www.clinicaltdd.com
Comments
Safety after first trimester well documented, including 7-year follow-up of
offspring.
May be associated with fetal growth restriction and neonatal bradycardia.
Few controlled trials, but long follow up with few adverse events
documented; may cause neonatal thrombocytopenia.
May cause fetal bradycardia; may impair fetal response to hypoxic stress;
possible risk for lower birth weight when started in first or second trimester
(especially atenolol).
May cause volume depletion and electrolyte disorders. May be useful in
combination with methyldopa and vasodilator to mitigate compensatory
fluid retention.
Leads to fetal loss in animals; human use in second and third trimester
associated with fetopathy, oligohydramnios, growth restriction, and
neonatal anuric renal failure, which may be fatal.
PHARMACOLOGIC MANAGEMENT OF PIH
Details are shown in Table 1.
BP Control
A major benefit of BP control is to reduce the prevalence
of severe hypertension and decrease the risk of maternal
and fetal complications.20,21 A common consensus among
national and international guidelines is to start medication
at BP ≥ 160/110 mmHg.21-23 Guidelines from the American
Heart Association/American Stroke Association suggest
considering pharmacologic therapy for BP at 150–159/100–
109 mmHg.22 However, the European Society of Cardiology
recommends treatment of BP ≥ 140/90 mmHg in women with
organ damage, symptoms or superimposed PIH on chronic
hypertension.11,24 In patients with PIH, reducing the risk of
maternal organ damage without affecting placental blood
flow is important. However, there is no evidence regarding
the target for BP control. In 2014, the Japanese Society of
Hypertension suggested a target SBP ≤ 160 mmHg, target
DBP ≤ 110 mmHg or a 15–20% decrease in the mean BP.25
A recent large clinical trial, the Control of Hypertension In
Pregnancy Study (CHIPS), demonstrated that women who
can maintain BP at 130–140/85 mmHg have fewer episodes
of severe hypertension in pregnancy.20 Importantly, there were
no adverse fetal effects in the lower-BP target group, which
challenged a previous concern that lowering BP to “normal”
might be associated with reduced fetal growth.26 The incidence
of preeclampsia is similar in women treated with a standard,
less tightly controlled DBP (100 mmHg) or tightly controlled
DBP (85 mmHg). The ACOG recommends therapy adjustment
to maintain BP at 120–160/80–105 mmHg during pregnancy.10
The target range is narrower in Canadian guidelines and is
divided further into 130–155/80–105 mmHg for women with
chronic hypertension without comorbidities, and < 140/90
mmHg if comorbidities are present.23
Clinical Trials in Degenerative Diseases  ¦  June ¦  Volume 3  ¦  Issue 2
[Downloaded free from http://www.clinicaltdd.com on Sunday, October 7, 2018, IP: 181.113.175.10]
Lin et al. / Clin Trials Degener Dis
Table 2: Drugs for PIH treatment in emergencies
Drug Dose
Labetalol Starting dose of 20 mg (intravenous), then 80 mg every 20-30 minutes, up to
maximum of 300 mg; or constant infusion of 1-2 mg/min
Nifedipine Tablets recommended only: 10-30 mg
Hydralazine 5 mg (intravenous or intramuscular injection), then 5-10 mg every 20-40
minutes; or constant infusion of 0.5-10 mg/h
Nitroprusside Constant infusion of 0.5-10 μg/kg/min
Note: All drugs listed meet the United States Food and Drug Administration classification.
Drugs for PIH treatment
Methyldopa
The α2 adrenergic receptor agonist methyldopa is used widely
as a sympatholytic drug. It is first-line treatment for PIH.27,28
Serious adverse effects on maternal or fetal conditions have not
been reported during 40 years of use. The recommended daily
dose of methyldopa is 0.5–3.0 g in 2–4 doses.29 Side-effects
include sleepiness, dry mouth, general malaise, hemolytic
anemia, and hepatopathy.
Hydralazine
Previously, the vasodilator hydralazine was recommended as
first-line treatment for severe hypertension in pregnancy.30,31
The common side-effects of this drug are headache, nausea,
and vomiting. According to a recently reported meta-
analysis, hydralazine is less effective than labetalol for PIH
in all aspects.32 The recommended daily dose is 50–300 mg
administered in 3–4 doses. Side-effects include hypotension
and neonatal thrombocytopenia.
Calcium-channel blockers
Calcium-channel blockers can be of two subtypes:
dihydropyridine (nifedipine) and non-dihydropyridine
(verapamil, diltiazem). Nifedipine is considered safe to use
in pregnancy.33 Calcium-channel blockers other than the long-
acting nifedipine should be used according to the physician’s
evaluation after full explanation of the necessity for treating
PIH and obtaining informed consent. Calcium-channel
blockers have not been recommended in guidelines because
of insufficient supporting evidence. The recommended starting
dose for nifedipine is 10-20 mg (p.o., t.d.s.) with a maximum
dose of 180 mg per day. The long-acting tablet formulation
of nifedipine is usually dosed once daily starting at 30–60 mg
and a maximum of 120 mg per day.34 Recently, nimodipine
(20–60 mg, p.o., b.d. or t.d.s.) and nicardipine (20–40 mg, p.o.,
t.d.s.) have been recommended for PIH by guidelines in China.
Beta-blockers (β-blockers)
Labetalol can blockade α1 adrenoreceptors to cause
vasodilation. It has a greater β-blocking effect than α-blocking
effect (3:1 ratio). Labetalol is first-line treatment for
hypertensive disease during pregnancy. It is used in widely
Europe, USA and China because it is considered safe.35,36
A meta-analysis demonstrated that labetalol has fewer
adverse effects on maternal conditions than hydralazine.32
Most β-blockers are contraindicated for pregnant women.
Therefore, if administration of other β-blockers is necessary,
Clinical Trials in Degenerative Diseases  ¦  June ¦  Volume 3  ¦  Issue 2
www.clinicaltdd.com
Comments
Lower risk of tachycardia and arrhythmia
compared with other vasodilators
Safe to use in labor
Long-term safety and efficacy
Possible cyanide toxiciy
then informed consent must be obtained after explaining the
reasons of treatment.
Diuretics
Diuretics can lead to reductions in the pre-eclampsia-
associated volume of: (i) circulating plasma; (ii) placental
blood flow. Therefore, diuretics should be avoided in patients
with pre-eclampsia. Diuretics can be used if pulmonary
edema or heart-failure signs are absent.37 For patients with
chronic hypertension who take diuretics before pregnancy,
the effect of reduction in placental blood flow is not apparent
if the drug is continued after pregnancy. A commonly used
diuretic is hydrochlorothiazide at a daily dose of 12.5–25 mg.
Spironolactone is not recommended because it has been found
to have an anti-androgenic effect during fetal development
in animal models, though it does not seem to induce adverse
outcomes in small cohorts of human participants.38 We do not
suggest spironolactone use in pregnant women, but it can be
used only if a potassium-sparing diuretic is needed.
Alpha-blockers (α-Blockers)
α-Blockers are not contraindicated for pregnant women or those
who may be pregnant, but use of α-blockers in this population
should be avoided. Only one study has recommended using
these drugs in pregnant women with hypertension secondary to
pheochromocytoma.39 Phentolamine is an α1 and α2 receptor
agonist recommended for use in Chinese guidelines in 2015.
Renin aldosterone system (RAS) blockers
There are three types of RAS blockers: angiotensin-converting
enzyme inhibitors, angiotensin-receptor blockers and direct
inhibitors of renin. These drugs are strictly contraindicated in
women who have been pregnant or are planning to become
pregnant. Use of any RAS blocker can lead to teratogenicity
and oligohydramnios during pregnancy.40,41
EMERGENCY TREATMENT OF PIH
Different countries have slightly different treatment strategies
for PIH, but the common agents are labetalol (i.v.), hydralazine
(i.v.), and nifedipine (p.o., s.l.).23,42 Nitroprusside is used rarely
during pregnancy because it can increase the risk of cyanide
intoxication in the fetus (Table 2).
CONCLUSION
PIH increases eclampsia risk and threatens maternal and
fetal health. In this review, we recommend treatment if BP
≥ 150/90 mmHg using labetalol, nifedipine, or methyldopa
85
[Downloaded free from http://www.clinicaltdd.com on Sunday, October 7, 2018, IP: 181.113.175.10]
Lin et al. / Clin Trials Degener Dis
given as first-line agents via the oral route. In the setting
of chronic hypertension, one agent should be administered
at the highest dose before combination with another agent.
Hypertension emergencies due to BP > 160/110 mmHg can
result in maternal stroke or eclampsia. If delivery is imminent,
parenteral therapy with labetalol (i.v.), hydralazine (i.v.) or
nifedipine (p.o.) is indicated.
Author contributions
Writing the manuscript: YL; supervising the study: YZ and YNJ;
proofreading: WS. All authors approved the final version of this
manuscript for publication.
Conflicts of interest
None declared.
Copyright license agreement
The Copyright License Agreement has been signed by all authors
before publication.
Plagiarism check
Checked twice by iThenticate.
Peer review
Externally peer reviewed.
Open access statement
This is an open access journal, and articles are distributed under
the terms of the Creative Commons Attribution-NonCommercial-
ShareAlike 4.0 License, which allows others to remix, tweak, and
build upon the work non-commercially, as long as appropriate credit
is given and the new creations are licensed under the identical terms.
References
1. Lackland DT, Weber MA. Global burden of cardiovascular
disease and stroke: hypertension at the core. Can J Cardiol.
2015;31:569-571.
2. Hernandorena I, Duron E, Vidal JS, Hanon O. Treatment
options and considerations for hypertensive patients to prevent
dementia. Expert Opin Pharmacother. 2017;18:989-1000.
3. Poulter NR, Prabhakaran D, Caulfield M. Hypertension.
Lancet. 2015;386:801-812.
4. Carretero OA, Oparil S. Essential hypertension. Part I:
definition and etiology. Circulation. 2000;101:329-335.
5. Simon AC, Levenson J, Bouthier J, Safar ME, Avolio AP.
Evidence of early degenerative changes in large arteries in
human essential hypertension. Hypertension. 1985;7:675-680.
6. O'Brien E, Beevers DG, Lip GYH. ABC of Hypertension.
London: BMJ Books; 2007.
7. Wallis AB, Saftlas AF, Hsia J, Atrash HK. Secular trends in the
rates of preeclampsia, eclampsia, and gestational hypertension,
United States, 1987-2004. Am J Hypertens. 2008;21:521-526.
8. Jiang YN, Song W. Blood pressure assessment and drug
selection in pregnancy-induced hypertension. Zhongguo Yixue
Qianyan Zazhi: Dianzi Ban. 2014;6:3-8.
9. Calhoun DA, Jones D, Textor S, et al. Resistant hypertension:
diagnosis, evaluation, and treatment. A scientific statement
from the American Heart Association Professional Education
Committee of the Council for High Blood Pressure Research.
Hypertension. 2008;51:1403-1419.
10. American College of Obstetricians and Gynecologists;
Task Force on Hypertension in Pregnancy. Hypertension in
pregnancy. Report of the American College of Obstetricians
and Gynecologists’ task force on hypertension in pregnancy.
Obstet Gynecol. 2013;122:1122-1131.
86
www.clinicaltdd.com
11. European Society of Gynecology (ESG); Association for
European Paediatric Cardiology (AEPC); German Society for
Gender Medicine (DGesGM), et al. ESC Guidelines on the
management of cardiovascular diseases during pregnancy: the
Task Force on the Management of Cardiovascular Diseases
during Pregnancy of the European Society of Cardiology
(ESC). Eur Heart J. 2011;32:3147-3197.
12. Committee Opinion No 652: Magnesium sulfate use in
obstetrics. Obstet Gynecol. 2016;127:e52-53.
13. Chapman AB, Abraham WT, Zamudio S, et al. Temporal
relationships between hormonal and hemodynamic changes in
early human pregnancy. Kidney Int. 1998;54:2056-2063.
14. Nahar L, Nahar K, Hossain MI, Yasmin H, Annur BM.
Placental changes in pregnancy induced hypertension and its
impacts on fetal outcome. Mymensingh Med J. 2015;24:9-17.
15. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-
eclampsia and risk of cardiovascular disease and cancer in later
life: systematic review and meta-analysis. BMJ. 2007;335:974.
16. ONTARGET Investigators, Yusuf S, Teo KK, et al. Telmisartan,
ramipril, or both in patients at high risk for vascular events. N
Engl J Med. 2008;358:1547-1559.
17. Olsen SF, Osterdal ML, Salvig JD, Weber T, Tabor A, Secher
NJ. Duration of pregnancy in relation to fish oil supplementation
and habitual fish intake: a randomised clinical trial with fish oil.
Eur J Clin Nutr. 2007;61:976-985.
18. Purswani JM, Gala P, Dwarkanath P, Larkin HM, Kurpad A,
Mehta S. The role of vitamin D in pre-eclampsia: a systematic
review. BMC Pregnancy Childbirth. 2017;17:231.
19. Magro-Malosso ER, Saccone G, Di Tommaso M, Roman A,
Berghella V. Exercise during pregnancy and risk of gestational
hypertensive disorders: a systematic review and meta-analysis.
Acta Obstet Gynecol Scand. 2017;96:921-931.
20. Magee LA, von Dadelszen P, Rey E, et al. Less-tight versus
tight control of hypertension in pregnancy. N Engl J Med.
2015;372:407-417.
21. Molvi SN, Mir S, Rana VS, Jabeen F, Malik AR. Role of
antihypertensive therapy in mild to moderate pregnancy-
induced hypertension: a prospective randomized study
comparing labetalol with alpha methyldopa. Arch Gynecol
Obstet. 2012;285:1553-1562.
22. Bushnell C, McCullough LD, Awad IA, et al. Guidelines for
the prevention of stroke in women: a statement for healthcare
professionals from the American Heart Association/American
Stroke Association. Stroke. 2014;45:1545-1588.
23. Magee LA, Pels A, Helewa M, Rey E, von Dadelszen P;
Canadian Hypertensive Disorders of Pregnancy Working
Group. Diagnosis, evaluation, and management of the
hypertensive disorders of pregnancy: executive summary. J
Obstet Gynaecol Can. 2014;36:416-441.
24. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC
guidelines for the management of arterial hypertension: the
Task Force for the Management of Arterial Hypertension of the
European Society of Hypertension (ESH) and of the European
Society of Cardiology (ESC). Eur Heart J. 2013;34:2159-2219.
25. Shimamoto K, Ando K, Fujita T, et al. The Japanese Society of
Hypertension Guidelines for the Management of Hypertension
(JSH 2014). Hypertens Res. 2014;37:253-390.
26. August P. Lowering diastolic blood pressure in non-proteinuric
hypertension in pregnancy is not harmful to the fetus and
is associated with reduced frequency of severe maternal
hypertension. Evid Based Med. 2015;20:141.
Clinical Trials in Degenerative Diseases  ¦  June ¦  Volume 3  ¦  Issue 2
[Downloaded free from http://www.clinicaltdd.com on Sunday, October 7, 2018, IP: 181.113.175.10]
Lin et al. / Clin Trials Degener Dis
27. Plouin PF, Breart G, Maillard F, Papiernik E, Relier JP.
Comparison of antihypertensive efficacy and perinatal safety
of labetalol and methyldopa in the treatment of hypertension
in pregnancy: a randomized controlled trial. Br J Obstet
Gynaecol. 1988;95:868-876.
28. Redman CW, Beilin LJ, Bonnar J. Treatment of hypertension
in pregnancy with methyldopa: blood pressure control and side
effects. Br J Obstet Gynaecol. 1977;84:419-426.
29. Anderson GD, Carr DB. Effect of pregnancy on the
pharmacokinetics of antihypertensive drugs. Clin
Pharmacokinet. 2009;48:159-168.
30. Report of the National High Blood Pressure Education Program
Working Group on High Blood Pressure in Pregnancy. Am J
Obstet Gynecol. 2000;183:S1-S22.
31. Brown MA, Hague WM, Higgins J, et al. The detection,
investigation and management of hypertension in pregnancy:
executive summary. Aust N Z J Obstet Gynaecol. 2000;40:133-
138.
32. Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen
P. Hydralazine for treatment of severe hypertension in
pregnancy: meta-analysis. BMJ. 2003;327:955-960.
33. Clark SM, Dunn HE, Hankins GD. A review of oral labetalol
and nifedipine in mild to moderate hypertension in pregnancy.
Semin Perinatol. 2015;39:548-555.
34. Bortolus R, Ricci E, Chatenoud L, Parazzini F. Nifedipine
administered in pregnancy: effect on the development of
children at 18 months. BJOG. 2000;107:792-794.
Clinical Trials in Degenerative Diseases  ¦  June ¦  Volume 3  ¦  Issue 2
www.clinicaltdd.com
35. Pickles CJ, Broughton Pipkin F, Symonds EM. A randomised
placebo controlled trial of labetalol in the treatment of mild
to moderate pregnancy induced hypertension. Br J Obstet
Gynaecol. 1992;99:964-968.
36. Pickles CJ, Symonds EM, Broughton Pipkin F. The fetal
outcome in a randomized double-blind controlled trial of
labetalol versus placebo in pregnancy-induced hypertension.
Br J Obstet Gynaecol. 1989;96:38-43.
37. Collins R, Yusuf S, Peto R. Overview of randomised trials of
diuretics in pregnancy. Br Med J (Clin Res Ed). 1985;290:17-
23.
38. Riester A, Reincke M. Progress in primary aldosteronism:
mineralocorticoid receptor antagonists and management
of primary aldosteronism in pregnancy. Eur J Endocrinol.
2015;172:R23-30.
39. Freier DT, Thompson NW. Pheochromocytoma and pregnancy:
the epitome of high risk. Surgery. 1993;114:1148-1152.
40. Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major
congenital malformations after first-trimester exposure to ACE
inhibitors. N Engl J Med. 2006;354:2443-2451.
41. Li DK, Yang C, Andrade S, Tavares V, Ferber JR. Maternal
exposure to angiotensin converting enzyme inhibitors in
the first trimester and risk of malformations in offspring: a
retrospective cohort study. BMJ. 2011;343:d5931.
42. Visintin C, Mugglestone MA, Almerie MQ, et al. Management
of hypertensive disorders during pregnancy: summary of NICE
guidance. BMJ. 2010;341:c2207.
87