Current Hypertension Reports (2020) 22:58

https://doi.org/10.1007/s11906-020-01058-w

PREECLAMPSIA (VD GAROVIC, SECTION EDITOR)

Postpartum Hypertension
V. Katsi 1 & G. Skalis 2 & G. Vamvakou 2 & D. Tousoulis 3 & T. Makris 2

# Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract
Purpose of Review Hypertension affects approximately 10% of pregnancies and may persist in the postpartum period.
Furthermore, de novo hypertension may present after delivery, but its exact prevalence is not verified. Both types of hypertension
expose the mother to eventually severe complications like eclampsia, stroke, pulmonary edema, and HELLP (hemolysis, elevated
liver enzymes, low platelet) syndrome.
Recent Findings Until today, there are limited data regarding the risk factors, pathogenesis, and pathophysiology of postpartum
hypertensive disorders. However, there is certain evidence that preeclampsia may in large part be responsible. Women who
experienced preeclampsia during pregnancy, although considered cured after delivery and elimination of the placenta, continue to
present endothelial and renal dysfunction in the postpartum period. The brain and kidneys are particularly sensitive to this
pathological vascular condition, and severe complications may result from their involvement.
Summary Large randomized trials are needed to give us the evidence that will allow a timely diagnosis and treatment. Until then,
medical providers should increase their knowledge regarding hypertension after delivery because many times there is an
underestimation of the complications that can ensue after a misdiagnosed or undertreated postpartum hypertension.

Keywords Postpartum . Hypertension . Preeclampsia . Eclampsia . Endothelial

Introduction worldwide [3]. Postpartum hypertension, both persistent and

Hypertensive disorders of pregnancy (HDP) complicate ap-
proximately 10% of all pregnancies and cause serious compli-
cations including maternal death [1]. Under the term hyper-
tensive disorders are found gestational hypertension, pre-
eclampsia, and eclampsia. Delivery is still considered thera-
peutic for these conditions, but growing evidence suggests
that postnatal persistent or de novo hypertension is more com-
mon and serious than initially believed and should be included
in this group [2]. The different expressions of the maternal
cardiovascular dysfunction constitute a serious threat during
pregnancy and the puerperium causing up to 18% of deaths
This article is part of the Topical Collection on Preeclampsia
* G. Skalis
gskalis@yahoo.gr
1
Cardiology Department, Hippokration Hospital, Athens, Greece
2
Department of Cardiology, Helena Venizelou Hospital,
Athens, Greece
3
1st Department of Cardiology, National and Kapodistrian University
of Athens, Athens, Greece
de novo, is a condition that can reproduce all the maternal
complications and negative outcomes that are observed ante-
natal [4]. However, the postnatal treatment is the same as
during pregnancy and even more efficient given the possibil-
ity to use every category of antihypertensive drugs if lactation
is abandoned [4].
Hypertension in Pregnancy and Postpartum
Hypertension in pregnancy is defined by blood pressure mea-
surements of systolic blood pressure (SBP) ≥ 140 mmHg and/
or diastolic blood pressure (DBP) ≥ 90 mmHg on two mea-
surements at an interval of 4 h [1]. SBP ≥ 160 mmHg and/or
DBP ≥ 110 mmHg on two measurements at 15–20 min apart
define severe hypertension and necessitate immediate treat-
ment in order to prevent serious complications [1]. Beyond
the mere numerical definition, hypertension in pregnancy is
classified in base of its chronicity and the complications asso-
ciated. According to ACOG’s classification hypertension in
pregnancy manifests as follows: (a) gestational hypertension
(GH) is characterized by de novo high blood pressure after
20 weeks of pregnancy without end-organ dysfunction, (b)
 58 Page 2 of 11
preeclampsia (PE) presents as a rise in blood pressure in a
normotensive pregnancy after the 20th week with evidence
of end-organ damage-like proteinuria, (c) chronic hyperten-
sion when high blood pressure is diagnosed before the 20th
week of gestation or persists for more than 12 weeks after
delivery, and (d) chronic hypertension with superimposed
PE [1]. GH and PE have many risk factors in common such
as overweight and obesity, twin birth, nulliparity, type 1 and 2
diabetes, and PE history [5]. However, remains to be
established whether they are different entities or part of the
same pathological process. Hypertension usually precedes
other clinical manifestations of PE but not all the GH evolve
to PE even if the rise in blood pressure occurs early in preg-
nancy [6]. Twin birth, a well-known common risk factor, has
greater impact on PE, while a preeclamptic pregnancy results
in a risk for GH which is twofold to PE [7].
For many years, delivery was considered as the only but
definite cure of HDP and that the whole pathological process
subsides mostly within 48 h after delivery [8]. Blood pressure
monitoring is frequently left out from the follow-up during the
puerperium because both the incidence and the clinical impor-
tance of postpartum hypertension are underestimated. Today,
it is known that some women continue to have hypertension or
present de novo and left it untreated which may cause severe
complications like stroke [9, 10]. The diagnosis of postpartum
hypertension is based on the same criteria used for hyperten-
sion in gestation [1]. A significant proportion (50%) of wom-
en with antenatal hypertension remain hypertensive after de-
livery, and about 10% of those with normotensive pregnancy
develop abnormal blood pressure (> 140/90 mmHg) in the
6 weeks following delivery [11]. Thrombotic events due to
the hypercoagulable state of pregnancy are more frequent
around delivery and within 6 weeks from delivery [12].
Furthermore, persistent and de novo hypertension highly in-
creases the risk for severe cerebrovascular complications [13].
As a result, pregnancy-associated stroke is more frequent dur-
ing the delivery and postpartum period especially in young
women where rarer mechanisms like arterial dissections, rup-
ture of arteriovenous malformations, cerebral venous throm-
bosis, and the reversible cerebral vasoconstriction may exist
[13–16].
The Blood Pressure in Pregnancy
In pregnancy occurs a significant adaptation of the maternal
cardiovascular physiology. The whole process is oriented to-
wards an increased cardiac output within physiologic limits of
blood pressure [17]. Peripheral vascular resistance drops sig-
nificantly in the first trimester and after a minimum in the
second trimester remains stable or increases slightly [18]. In
the postpartum period, peripheral resistances return to near
normal with complete restauration in the following 2 weeks
[19]. Cardiac output increases by 45% in a singleton
Curr Hypertens Rep (2020) 22:58
pregnancy and by 60% in a twin one [20]. The parallel vaso-
dilation that occurs in the kidneys results in a 50% higher
glomerular filtration rate and consequently low serum levels
of creatinine, uric acid, and urea [21]. The higher cardiac
output is sustained by the increased stroke volume in the first
trimester while later is primarily maintained by the increased
heart rate [20]. Given the increase in cardiac output, low level
peripheral resistance is crucial for the maintenance of low and
normal blood pressure values. The maternal endocrine system
is at the base of the cardiovascular adaptation with increased
levels of estrogen, relaxin, and progesterone in the first trimes-
ter [17, 22–24]. Relaxin is a hormone released by the corpus
luteum and rises significantly once conception takes place and
after an early peak falls to intermediate levels [25]. Relaxin
induces vasodilation through endothelium-released nitric ox-
ide [24, 26]. Furthermore, relaxin might play an important role
in preeclampsia as it appears to influence all the pathophysi-
ologic aspects of this hypertensive disorder [25]. In fact, preg-
nant mice which are deficient in relaxin present proteinuria,
increased sensitivity to angiotensin, endothelin, and other va-
soconstrictors with resultant hypertension [25, 27–29].
Finally, a deficit in relaxin causes stiffer uterine arteries in
pregnant mice [30] Interestingly, the hemodynamics effects
of this hormone are not limited in pregnancy but are also
effective out of gestation [31]. On the other hand, the low
peripheral resistance and the increased vessel capacity bring
forth the renin-angiotensin-aldosterone system (RAAS) which
rises significantly and sustains the increase in plasma volume
[32]. However, the hypertensive effect of the increased RAAS
activity is counterbalanced by a reduced sensitivity to its com-
ponents [33].
Pathophysiology of Hypertension in Pregnancy and
Postpartum
Although the mechanisms responsible for the cardiovascular
adaptation in pregnancy are well known, pregnancy-induced
hypertension poses significant difficulties regarding its path-
ophysiology and its clinical manifestations. The hemodynam-
ic changes are not adequate or are absent, and consequently,
there is an elevated peripheral resistance, reduced renal perfu-
sion, and glomerular filtration [34, 35]. The initial step to
hypertension in pregnancy is a reduced perfusion of the pla-
centa which results in maternal endothelial dysfunction, hy-
pertension, and preeclampsia [36, 37]. However, although it is
a well-accepted initial mechanism, there is evidence that sub-
stantial difference exists between gestational hypertension and
preeclampsia. Hypoperfused placenta is the product of incom-
plete remodeling of the spiral arteries and the consequent
problematic placentation. Syncytial knots, fibrin deposits,
and high resistance flow in the uterine arteries are character-
istics of the ischemic placenta but are constantly found in
preeclampsia rather than in gestational hypertension [38].
Curr Hypertens Rep (2020) 22:58
Furthermore, the hypoperfused placenta releases
antiangiogenic factors which play a major role in the maternal
syndrome. While in normal pregnancy, angiogenesis is
sustained by increased levels of vascular growth factor
(VEGF) and platelet growth factor (PIGF) with low levels of
their antagonist soluble fms-like tyrosine kinase (sFlt-1,), and
in PE occurs the inverse with high ratio sFilt-1/PIGF [39].
Interestingly, the prevalence of antiangiogenic factors is typi-
cally high in early PE (˂ 34 weeks of gestation) but blunted in
late PE (> 34 weeks), while they are not found in GH [37, 39].
In the postpartum, the plasma volume overload condition of
normal pregnancy can be further exaggerated by the adminis-
tration of significant volume of fluids during delivery, in par-
ticular in case of spinal anesthesia and cesarean section [40].
Moreover, administration of nonsteroidal anti-inflammatory
drugs like indomethacin and ibuprofen is another potential
cause of blood pressure increase due to the sodium and water
retention that these substances promote [41]. Finally, the use
of ergot alkaloids like ergometrine and methylergonovine for
uterine atony can increase and/or exacerbate a preexisting
borderline blood pressure [4].
Postpartum Hypertension
The majority of postpartum hypertension cases are due to
gestational or chronic hypertension and preeclampsia with
persistent high blood pressure after delivery. Although elimi-
nation of the placenta is therapeutic for these conditions, the
return of blood pressure to normal levels may take a certain
time. In fact, 50–85% of hypertensive pregnancies are expect-
ed to normalize by day seven postdelivery [42]. Beyond the
first week, hypertension related to pregnancy may persist until
6 to 12 weeks before the eventual resolution. This occurs more
frequently in women with preeclampsia, high body mass in-
dex, early gestational hypertension, and/or high systolic and
diastolic blood pressure [43, 44]. Naturally, those with
preexisting hypertension will continue to have high blood
pressure, and in total, about 25% of women with hypertensive
disorders of pregnancy will need antihypertensive treatment
2 years after the completion of pregnancy [43, 44].
Preeclamptic women tend to present a decrease with fre-
quent normalization of their blood pressure in the first 2 days
after delivery, but a rise follows towards antenatal levels 3–
6 days in the puerperium [45]. Furthermore, in the majority of
these women, hypertension persists until at least 16 days after
giving birth, while in gestational hypertension, normalization
comes earlier [46].
De novo postpartum hypertension is a well-known but
underestimated clinical condition. As the majority of the
women who were normotensive until peripartum are
reexamined at 6 weeks after delivery, many cases with mild
asymptomatic hypertension are missed, and only those who
are complicated by significant symptoms like headache and
Page 3 of 11 58
blurred vision or dyspnea are usually evaluated in the emer-
gency department and if not hospitalized are not registered.
Furthermore, the majority of the studies consider the period
between 2nd and 6th day after the delivery or those women
who are hospitalized de novo [9, 46–48]. In addition, the
absence of multicenter studies makes quite difficult a precise
estimation of de novo postpartum hypertension which ranges
from 0.3 to 7.5% [4]. Regarding de novo postpartum hyper-
tension, plasma volume overload as occurs in normal preg-
nancy and large volume of fluids given peripartum can cause a
substantial increase in blood pressure, particularly when there
is not normal renal function [42]. As a result, a transient rise in
BP may derive, or preexistent subclinical PE may be
unmasked, but also delayed postpartum preeclampsia can be
the cause of the hypertension [1, 4, 11].
Finally, postpartum hypertension might be secondary to
primary hyperaldosteronism, pheochromocytoma, hyperthy-
roidism, and renal artery stenosis [4]. Table 1 shows the po-
tential causes of hypertension after delivery.
Postpartum and Preeclampsia
Preeclampsia is straightly tied to postpartum hypertension,
and its pathogenesis continues to be a mystery. Even today
remains unclear whether there are different types of PE with
eventually distinct pathogenetic mechanisms. In fact, PE can
be early (≤ 34 weeks of gestation), late PE (>34 weeks), or
delayed postpartum PE (within 6 weeks) [1]. Furthermore, PE
appears to be independent from GH and not a more severe
stage of it. Current evidence indicates that these hypertensive
disorders of pregnancy have common risk factors but also
present substantial epidemiological and pathophysiological
differences. For example, the probability that gestational hy-
pertension (GH) may reoccur is higher (20% to 47%) than that
for preeclampsia (5% to 10%) [49].
A retrospective study of 150 pregnant women detected
vascular pathology in the decidua and infarcted villi in a sig-
nificantly higher number of preeclampsia than in GH (47% vs
33%) and (50% vs 38%), respectively [50]. Furthermore, the
well-established antiangiogenic profile of PE with a high ratio
sFlt1/PIGF is not observed in GH [39, 51]. In the same
Table 1 Potential causes of postpartum hypertension
Preeclampsia persistent after delivery
Preeclampsia non diagnosed during pregnancy
Preeclampsia with postpartum clinical presentation (?)
Gestational hypertension persistent after delivery
Chronic hypertension primary or secondary
Postpartum hypertension due to volume overload, pain, NSAIDs (?);
expected to be transient
Postpartum thyroiditis with transient hyperthyroidism
 58 Page 4 of 11
direction, flow-mediated dilatation in GH is not different from
normotensive women while is abnormal in preeclamptic preg-
nancies [50, 52]. Overall, even if there is no extended study of
the hypertensive disorders of pregnancy and their eventual
specific characteristics, it is logical to consider them as two
different entities and not as two stages of the same patholog-
ical process. PE presents maternal endothelial dysfunction and
predominance of antiangiogenic factors with frequent end-
organ impairment, while GH appears to be an insufficient
vascular adaptation to the increased blood volume and high
cardiac output that are characteristics of pregnancy. Moreover,
preeclampsia is characterized by a reduced maternal blood
volume and increased vascular resistance, and these changes
precede several weeks of the clinical manifestations of the
syndrome [51–54]. Concluding, early onset/severe PE has
more solid pathophysiological basis that is less depended on
the physiological changes of pregnancy, and as such delivery
and exportation of placenta may not result in complete reso-
lution. Therefore, it is not surprising the fact that the incidence
of delayed (within 6 weeks) postpartum preeclampsia is 6%
[48].
In a retrospective cohort study were included 62 normoten-
sive women who developed hypertension during pregnancy,
within 3 days after delivery, and after the third day [9]. The
majority, 81%, of the 62 women had their blood pressure
normalized by the end of the third month after delivery with
meantime 5.4 ± 3.7 weeks [9].Two women experienced nor-
malization of the BP beyond the 3 months postpartum, and
their follow-up resulted in the diagnosis of hypertension later
in life. In 12 women (19%), arterial hypertension persisted
after 6 months and was considered chronic hypertension.
Factors associated with persistent hypertension were as fol-
lows: (1) advanced age of the mother (38.8 years vs 34.4, p =
0.018) and (2) early onset of hypertension and consecutively
longer duration of hypertension before delivery. In this series,
further analysis showed some interesting facts-findings.
Although chronic preexisted hypertension is considered the
one diagnosed before the 20th week of gestation, of the 12
cases only, 4 presented high blood pressure between 10 and
17 weeks of gestation, while the majority was diagnosed from
22th to 39th week [9]. Interestingly, the development of PE/
HELLP syndrome after delivery was not associated with per-
sistent hypertension.
In another prospective cohort study was assessed the im-
pact of PE on arterial blood pressure in the postpartum be-
tween 6 and 12 weeks [53]. The assessment consisted in am-
bulatory blood pressure monitor (ABP) and revealed the dif-
ferent phenotypes of blood pressure after a pregnancy compli-
cated by PE. The study compared 115 women with diagnosed
preeclampsia vs 41 women normotensive during pregnancy at
6 to 12 weeks after delivery. The number of preeclamptic
women with hypertension as measured at office was 66
(57.4%) at the moment of the study [53]. Both office and
Curr Hypertens Rep (2020) 22:58
ABP were significantly higher in the preeclampsia group.
Diurnal ABP was (118.9 ± 15.0/83.2 ± 10.4 mmHg) vs
(104.8 ± 7.9/71.6 ± 5.3 mmHg; p ˂ 0.001). In the same direc-
tion, nighttime ABP measurements confirmed higher values
for the preeclampsia group (111.2 ± 17.6/74.8 ± 11.0 mmHg)
vs (94.3 ± 7.6/61.7 ± 4.6 mmHg; p ˂ 0.001) [53]. A very in-
teresting finding regarded the group with preeclampsia that
was not under treatment for hypertension (84/115). In this
group, hypertension was confirmed in 20 women (23.8%)
with ABP values ≥ 135/85 mmHg. Moreover, there were a
significant number of women with masked hypertension. In
fact, in 13 (11.6%) preeclamptic women with normal office
blood pressure, ABP revealed abnormal values [53]. Masked
hypertension is a very important issue due to the increased risk
of hypertensive complications related to preeclampsia in post-
partum preeclamptic women who eventually were classified
as cured. In addition, masked hypertension may contribute to
the higher cardiovascular risk with which PE aggravates the
future of these women.
In this prospective study, two more disturbances of the
arterial pressure were described. Firstly, the ABP showed that
the majority (59.8%) of the women with preeclamptic preg-
nancy had a non-dipping profile. Of note, also the control
group showed absence of nocturnal dipping. Breastfeeding,
for both groups, may well explain in part this finding due to
sleep disruption. However, absolute nocturnal BP was signif-
icantly higher in the preeclampsia group (111.2 ± 17.6/ 74.8 ±
11.0 mmHg) vs (94.3 ± 7.6/ 61.7 ± 4.6 mmHg) [53]. The ab-
normal non-dipper status has been observed in women at
10 years after a preeclamptic pregnancy [54].
Finally, 48.6% of the PE group presented high salt sensi-
tivity risk (RSS) versus 17.15% in the control group (p ˂ 0.01)
[54]. A high salt sensitivity is associated with abnormal noc-
turnal blood pressure possibly because of a pressure natriure-
sis curve shifted to the right at night in a damaged kidney with
reduced diurnal excretory capacity [55–57]. In support of
these results comes another study that followed 200 women
with severe preeclampsia for 12 months after delivery [58].
Also this study used ambulatory blood pressure monitor and
confirmed the importance of this method for the evaluation of
women in the postpartum. The results showed that 41.5% of
the women had hypertension 1 year after delivery and 17.5%
of them had masked hypertension [58]. This study confirms
the high prevalence of postpartum hypertension among pre-
eclamptic women and underlines the importance of ABPM for
the detection of masked hypertension.
Another large, actually the largest until today, observation-
al clinical study took in examination postpartum hypertension
[2]. In this series, 988 consecutive women who delivered with
cesarean section in a tertiary hospital were studied with regard
to blood pressure ante- and postpartum. In addition, known
angiogenic factors like soluble fms-like tyrosine kinase 1
(sFlt1) and placenta growth factor (PIGF) associated with
Curr Hypertens Rep (2020) 22:58
PE were measured. There were 774 women with normal blood
pressure during pregnancy, and 77 (9.9%) of them developed
de novo hypertension after delivery, while 107 (50.0%) of 214
with hypertensive pregnancies did not normalize their BP after
delivery [2]. Interestingly, the two groups shared diabetes
mellitus and higher BMI at delivery as factors predisposing
to hypertension in the postpartum. High levels of sFlt1, low
levels of PIGF, and a high ratio aFlt1/PIGF were also posi-
tively correlated with the development or persistence of hy-
pertension in the puerperium. In addition, higher levels of
systolic and diastolic pressure appeared to predict abnormal
levels of arterial blood pressure in both groups [2]. On the
other hand, intraoperative and postoperative administration
of fluids although it was no different in the two groups did
not associate with hypertension. Also, nonsteroidal analgesic
given in more than 90% of all patients did not increase the
incidence of postpartum hypertension.
The higher levels of BP, diabetes mellitus, and increased
BMI in combination with the specific antiangiogenic profile
sustain the hypothesis that de novo postpartum hypertension is
a form of subclinical or late onset (after delivery) PE with
hypertension as its clinical manifestation. In the same direc-
tion, persistent hypertension could be the consequence of se-
vere preeclampsia.
Secondary Hypertension
Hypertension in pregnancy can be secondary to any patholog-
ical process that is responsible for an increase in blood pres-
sure. Postpartum hypertension may also be secondary and
should be highly suspected as such when blood pressure is
particularly increased and resistant to treatment. Renal disor-
ders including fibromuscular dysplasia of the renal arteries,
primary hyperaldosteronism, Cushing’s syndrome, and pheo-
chromocytoma (a rare but not to be missed cause of hyperten-
sion), and transient hyperthyroidism in the context of postpar-
tum thyroiditis should be considered as possible underlying
mechanisms of a severe and resistant postpartum hyperten-
sion. Renal disease although uncommon is not rare. In a study
were examined women with preeclampsia and gestational hy-
pertension between 3 and 60 months after delivery. In both
groups, 2% of the women who were diagnosed with hyper-
tension had underlying kidney disease [59]. Therefore, urinal-
ysis, urine microscopy, serum creatinine, and renal imagining
should be performed in any hypertension that presents de
novo postpartum or persists beyond 6 weeks after delivery
[60].
In the same direction, serum electrolytes and in particular
potassium levels could be of importance in the diagnosis of
primary hyperaldosteronism. Thyroiditis which develops
postpartum is usually observed in patients with type I diabetes
mellitus. It is a Hashimoto similar entity which leads to hypo-
thyroidism, but a transient phase of overactive thyroid may
Page 5 of 11 58
precede, and thus hypertension due to hyperdynamic circula-
tion may result [61]. In that case, hypertension is accompanied
by tremor, nervousness, heat intolerance, and palpitations, and
a beta-blocker is the antihypertensive of choice [40].
Paroxysmal hypertension should prompt the diagnostic
process for pheochromocytoma, while low serum potassium
indicates the possibility of primary hyperaldosteronism [40,
60]. However, given the physiological adaptation of the car-
diovascular system to the pregnancy, many tests (urinary so-
dium excretion, serum aldosterone, renin activity measure-
ment in plasma) may be unreliable up to 1 month postdelivery
[40].
NSAIDS and Hypertension in Postpartum
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely
used for pain relief, and postpartum is a period where the need
for these drugs is increased. Furthermore, apart from the pain
that follows a natural delivery, cesarean section (obligatory for
premature termination of gestation due to hypertensive disor-
ders) significantly increases the need for pain relief. NSAIDs
are very suitable given their effectiveness, the lack of the
addictive effect of the narcotics, and their breastfeeding com-
patibility [62]. On the other hand, they are associated with a
hypertensive effect on patients with chronic hypertension
[63]. Hypertensives chronically treated with beta-blockers
and angiotensin-converting enzyme inhibitors are more sus-
ceptible to an increase in blood pressure under treatment with
NSAIDs [64]. Probably, this is due to inhibited synthesis of
prostaglandins with vasodilating effect and increased renal
retention of sodium secondary to reduced E2 prostaglandin
[65, 66]. Therefore, their use is not suggested in hypertensive
women in the postpartum period [67].
A retrospective cohort study examined the effect of ibupro-
fen (a commonly used NSAID) on the blood pressure of se-
vere preeclamptic women and whether its use would be asso-
ciated with persistent postpartum hypertension [68]. In the
study were included 324 women with severe PE antepartum
and hypertension 24 h after delivery. NSAIDs were adminis-
tered to 243 while 81 received different analgesic treatment.
The primary outcome of persistent significant hypertension (≥
150/100 mmHg) was not different in the two groups (70%
compared with 73%; adjusted OR 1.1, 95% CI 0.6–2.0)
[68]. Furthermore, secondary end points like pulmonary ede-
ma, renal dysfunction, intensive care unit admission, and
eclampsia, all possible severe complications of aggravating
postpartum hypertension, were equally occurred [68]
In another double-masked, randomized, controlled trial,
ibuprofen was tested vs acetaminophen in women with severe
antepartum preeclampsia. High doses of both were adminis-
tered between 6 h after delivery up to discharge [69]. Primary
end point was the duration of severe hypertension (≥ 160/
110 mmHg). Again, in this trial, there was no difference
 58 Page 6 of 11
between the two analgesics (ibuprofen vs. acetaminophen
35.3 vs 38.0 h, p = 0.30) [69]. Secondary outcomes like dura-
tion of hospital stay, need for additional antihypertensives,
need for further analgesic, or the duration of blood pressure
levels ≥ 150/100 mmHg were equally distributed in the two
groups [69].
Although there is a solid theoretical basis for concern about
the use of NSAIDs for pain control in the context of pre-
eclampsia/eclampsia, there is certain evidence at least for ibu-
profen that its use may be safe. The two aforementioned stud-
ies should be confirmed by larger randomized trials.
Salt Sensitivity After Hypertensive Disorder of
Pregnancy
Another important issue regarding preeclamptic women after
delivery is the increased cardiovascular risk that hypertensive
disorders of pregnancy are associated with [70]. Salt sensitiv-
ity is generally defined as an increase in office blood pressure
of 5% to 10% or mean ambulatory blood pressure (ABP)
increased by at least 4 mmHg after increment of salt consump-
tion [71]. Women are salt insensitive and change their status
after menopause indicating an age and hormonal effect [72].
In a prospective study, 21 pre-menopausal women with a his-
tory of severe PE were compared with 19 controls 5–10 years
after the index pregnancy [54]. Exposed to high-salt diet,
women with previous PE showed a significant increase in
daytime ambulatory blood pressure (115 [109–118]/79
[73–79] mmHg on low salt to 123 [116–130/80 [73–81]
mmHg on high-salt diet) vs (111 [104–119]/77 [71–79, 82,
83] mmHg on low salt to 111 [106–116/75 [71–76, 82, 83]
mmHg on high-salt diet, p < 0.05). In accordance with these
findings, office blood pressure changed in the same direction
[54]. Also, the expected night fall in mean ABP was not in-
fluenced by high-salt diet in controls, while there was a reduc-
tion in women with a history of PE [54].
The adverse effect of a high-salt diet on arterial blood pres-
sure is well recognized although it is not valid for every indi-
vidual as salt-resistant cases are not uncommon [82]. A high-
salt diet apart from the gradual increase in blood pressure
appears to cause cardiac hypertrophy even in the absence of
a hypertensive effect [83]. The altered physiology of sodium
was also observed with ABP in the early postpartum period
[53]. It would be logical to assume a significant early and
continuous negative effect of PE on dietary salt and arterial
blood pressure.
Although it has not been studied whether salt sensitivity is
a necessary condition for PE to be established which in that
case would preexisted to pregnancy, certain findings are char-
acteristics of PE and could relate with the development of salt
sensitivity [54]. PE and GH present higher sensitivity to an-
giotensin II ante- and postpartum [74]. Furthermore, alteration
of nitric oxide (NO) synthesis and metabolism occurring
Curr Hypertens Rep (2020) 22:58
during PE persist for 12 months after delivery and may con-
tribute to salt sensitivity and the maintenance of increased
blood pressure [75]. Finally, the reduced dipping of blood
pressure during nighttime is indicative of a defect in renal
handling of Na, and that abnormalities regarding the kidney
in preeclamptic women may persist beyond pregnancy [43].
Management of Postpartum Hypertension
Given that the basis for an appropriate management is a timely
diagnosis, increased awareness and a high grade of suspicion
are necessary in order to avoid a late diagnosis and the risk of
severe complications. Truth is that in practice after delivery in
hospital, care extends for 2 or 4 days depending on the ap-
proach (natural or cesarean section). As a result, a woman with
a normotensive pregnancy is not scheduled for a new evalua-
tion for many days, and a de novo hypertension could be
missed.
Generally blood pressure tends to be higher and occasion-
ally registers hypertensive values in normotensive women in
the puerperium [76]. Healthcare personnel should be aware of
this physiological condition so as to avoid unnecessary treat-
ment [61, 79]. As mentioned before, in hypertensive pregnan-
cies, blood pressure after an eventual drop in the first 48 h is
expected to rise to the antepartum values [47]. Normalization
of BP is expected earlier (average time 6 days) for GH than PE
(average time 16 days) [46]. While for women with hyperten-
sive pregnancy, postpartum hypertension is expected, and the
challenge consists in recognizing the real normotensive wom-
en with transient hypertension secondary to postpartum phys-
iological adaptation and medical interventions from those who
present de novo hypertension. Further investigations should
differentiate them in late postpartum PE, chronic hypertension
missed during pregnancy, or secondary to a pathological pro-
cess. Finally, there should also be awareness that any hyper-
tensive disorder of the postpartum could present the same
severe complications observed during pregnancy and that
these complications may be the first manifestation and the
cause for the postpartum medical contact.
To this end, blood pressure should be measured within 6 h
of the delivery and at the end of the first 48 h. In women with
hypertensive pregnancy, BP should be measured on a regular
basis between the 3rd and the 6th day even if presented nor-
motensive immediately after delivery and monitored closely
for other manifestations of severe PE (platelet count
˂ 150000, hyperuricemia, increased serum creatinine, abdom-
inal pain, vomitus, vision impairment, headache). Women
with normotensive pregnancies and hypertension in the first
48 h or later should be assessed like the aforementioned group
in order to exclude postpartum PE.
Women with risk factors for postpartum hypertension
(overweight, advanced age, diabetes mellitus) should be in-
formed for their risk and that their BP should be measured at
Curr Hypertens Rep (2020) 22:58 Page 7 of 11 58

home on a regular basis for 4 weeks. However, our position is
that all pregnant women should be aware of the risk for hy-
pertension and associated complications especially in the
puerperium.
In case of hypertension with high measurements and poor
response to treatment, secondary hypertension should be
suspected and 24-h urine sample for catecholamines and
metanephrines for those at low risk and plasma metanephrine
testing for those at high risk (family history, genetic profile)
[77]. Another important aspect of pheochromocytoma is that
part of its symptomatology like headaches, palpitations, nau-
sea, anxiety, and epigastric pain may be confused for severe
PE.
Antihypertensive Drugs
In postpartum, the diagnosis of hypertension does not differ
from that during pregnancy, and persistence of systolic BP >
140 and/or diastolic BP >90 mmHg for 4 h is diagnostic [1]. In
case of systolic BP ≥ 160 and/or diastolic BP ≥ 100 mmHg per-
sistent for at least 15 min, immediate treatment is necessary [1]
Without concern for the fetus, the treatment of the hyper-
tensive mother is easier than in the antenatal period. There is a
larger number of antihypertensive drugs to choose from with
no risk to cause placental hypoperfusion due to low BP
(˂ 110/70 mmHg). On the other hand, the breastfeeding com-
patibility of the antihypertensive drugs must be considered.
Treatment should be started at values > 150/100 mmHg [1].
In case of BP that does not exceed these values, treatment is
not necessary, with the admission that BP will be monitored
on a regular basis. However, this is mostly true for those
women who present de novo hypertension after delivery,
and it could be transient or mild, while in those with preexis-
tent GH or PE, treatment should be continued when BP mea-
surements are steadily 145–150/95–100 mmHg.
Methyldopa is credited as the safer among the antihyper-
tensive drugs in the antenatal period. However, side effects
like weakness at high dose and depression [78] in a population
already subjected to psychological discomfort because of pu-
erperium are sufficient to discourage its use after delivery.
Beta-blockers, calcium antagonists, and angiotensin-
converting enzyme (ACE) inhibitors are the drugs used.
Breastfeeding puts some limits regarding the substances
that can be prescribed. There are several factors that influence
the passage of a drug into human milk: lipid solubility, degree
of ionization, protein binding, molecular weight, half-life,
pKa, volume of distribution, and time between breastfeeding
and drug intake [79].
Nifedipine is the calcium antagonist most used and has
been proved safe both in pregnancy and lactation [80]. It can
be used as a slow release tablet and as a capsule with rapid
antihypertensive effect. The latter is very effective in hyper-
tensive emergencies especially when an intravenous line is not
established. Furthermore, as there is no concern of

Table 2 Antihypertensive drugs used in breastfeeding

Antihypertensive drugs used in breastfeeding

Drug Dose Contraindications Side effects/comments

Chronic treatment
Calcium channel antagonists
Nifedipine 30–60 mg × 1 Advanced aortic stenosis Headache, flushing, reflex
(extended release) tachycardia, palpitations
Amlodipine 10 mg × 1 As with nifedipine Same as with nifedipine may
be not so frequent/less
experience with breastfeeding
α/β-blockers Heart failure, asthma, Fatigue, postural hypotension/1st
Labetalol 100 mg × 2–200 mg × 4 mg bradycardia/atrioventricular block choice in thyroiditis
Atenolol 25–100 mg once daily
ACE inhibitors
Enalapril 5–20 mg × 2 Renal dysfunction Cough/first choice in chronic
Captopril 25–50 mg × 2–3 hypertension treated with ACEI
before pregnancy
Acute treatment
Nifedipine 5–10 mg, repeated at 20–30 min intervals if As chronic treatment Must be swallowed, not
necessary punctured or sublingually
Labetalol 20 mg IV repeated at 20 min intervals As chronic treatment As chronic treatment
Hydralazine 5–10 mg IV or IM repeated at 20–30 min Tachycardia Headache, tachycardia/arrhythmias
intervals if necessary
 58 Page 8 of 11
hypotension and consequently placental hypoperfusion, its
use should be more widespread [1]. Finally, there is no evi-
dence that the combination of nifedipine and magnesium in-
creases the risk of magnesium serious side effects like pro-
found hypotension and neuromuscular blockade [81].
Amlodipine, another calcium antagonist, passes in small
amounts in milk and appears to be safe in lactation [84].
Labetalol is a combined α1-β-adrenoceptor antagonist and
efficient antihypertensive that can be used as a chronic treat-
ment or intravenously in emergencies [1]. Its concentration in
human milk varies because of its short half-life and the fre-
quent daily dosage but is considered safe in lactation [80].
Metoprolol, a selective beta-blocker, accumulates in milk
but poses no problem for the newborn with normal liver func-
tion [85]. Hydralazine, a direct arteriolar vasodilator mainly
used parenterally in the treatment of high blood pressure, is
considered compatible with breastfeeding [83].
Angiotensin-converting enzyme inhibitors (ACEIs) are ab-
solutely contraindicated in pregnancy, but captopril and enal-
april are compatible with breastfeeding [80, 86]. ACEIs are
indicated in hypertensives with diabetes. Thiazide diuretics
are not indicated for chronic treatment because of the interfer-
ence with plasma volume and risk of suppressing lactation
[87]. Chlorothiazide, hydrochlorothiazide, bendro
flumethiazide, and chlorthalidone are considered compatible
with breastfeeding [80]. Furosemide can cause the same side
effects as thiazides but is the diuretic of choice in case of
volume overload, congestive heart failure, and pulmonary
edema.
Regarding the best treatment for postpartum hypertension,
we must distinguish between acute severe hypertension and
persistent postpartum hypertension. Two trials examined
eventual differences in the emergency setting. In one study,
IV hydralazine was compared with IV labetalol and was found
no difference in efficiency or side effects in women with post-
partum severe hypertension [88]. The second study tested IV
labetalol vs oral fast-acting nifedipine and found no substan-
tial difference apart from a faster antihypertensive effect ob-
tained with nifedipine [89, 90].
One randomized trial took place in the setting of postpar-
tum persistent hypertension (≥ 150/100 mmHg) in women
with antenatal PE, GH, or chronic hypertension and compared
oral labetalol with oral nifedipine [91]. The study is of impor-
tance as it compared the two most commonly used antihyper-
tensives in the postpartum period. There were no significant
differences except that labetalol controlled hypertension with
the initial dose more often and had less minor side effects [91].
Magnesium sulfate is not considered an antihypertensive
drug although has such an effect, and its use in BP > 160/
110 mmHg is obligatory in order to avoid eclamptic fits.
However, while in pregnancy the risk of seizures reduces by
at least 50%, there is not enough evidence of an equivalent
efficacy in the postpartum [92]. Also, there is an open debate
Curr Hypertens Rep (2020) 22:58
on the best regimen to apply after the standard loading dose
(magnesium sulfate IV to continue for 6, 12, or 24 h) [93].
Table 2 shows the drugs commonly used in postpartum
hypertension.
Conclusion
Postpartum hypertension is an important clinical entity that
increases the risk for severe complications after delivery.
However, it is frequently missed when presents after hospital
discharge. Increased awareness of medical providers who
might encounter these women should be a goal for the medical
community. Multicenter randomized studies are necessary in
order to shed light to epidemiological, clinical, and therapeutic
aspects. Preeclampsia appears to be at the basis of postpartum
persistent or de novo hypertension. Furthermore, endothelial
and renal dysfunction due to PE significantly increases the
risk in young premenopausal women.
Compliance with Ethical Standards
Conflict of Interest The authors declare that they have no conflict of
interest.
Human and Animal Rights and Informed Consent This article does not
contain any studies with human or animal subjects performed by any of
the authors.
References
Papers of particular interest, published recently, have been
highlighted as:
• Of importance
•• Of major importance
1. American College of Obstetricians and Gynecologists: TaskForce
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:
1122–31.
2. Goel A, Maski M, Baijracharva S, Wenger J, Zhang D,Salahuddin
S. Epidemiology and mechanisms of de novo and persistent hyper-
tension in the postpartum period. Circulation. 2015; 132(18): 1726–
1733 doi:https://doi.org/10.1161/CIRCULATIONAHA. . 115.
015721.
3. Magee L, von Dadelszen P. Prevention and treatment of postpartum
hypertension. Cochrane Database Syst Rev. 2013;4:CD004351.
4. Sibai BM. Etiology and management of postpartum hypertension-
preeclampsia. Am J Obstet Gynecol. 2012;206:470–5. https://doi.
org/10.1016/j.ajog.2011.09.002.
5. Poon LC, Kametas NA, Chelemen T, Leal A, Nicolaides KH.
Maternal risk factors for hypertensive disorders in pregnancy: a
multivariate approach. J Hum Hypertens. 2010;24(2):104–10.
https://doi.org/10.1038/jhh.2009.45.
Curr Hypertens Rep (2020) 22:58
6. Saudan P, Brown MA, Buddle ML, Jones M. Does gestational
hypertension become pre-eclampsia? Br J Obstet Gynaecol.
1998;105(11):1177–84.
7. Shen M, Smith GN, Rodger M, White RR, Walker MC, Wen SW.
Comparison of risk factors and outcomes of gestational hyperten-
sion and pre-eclampsia. PLoS One. 2017;12:e0175914.
8. Chelsey LC. Blood pressure, edema and proteinuria in pregnancy.9
.Proposal for classification. Prog Clin Biol Res. 1976;7:249–68.
9. Podymow T, August P. Postpartum course of gestational hyperten-
sion and preeclampsia. Hypertens Pregnancy. 2010;29:294–300.
https://doi.org/10.3109/10641950902777747.
10. Kuklina EV, Tong X, Bansil P, George MG, Callaghan WM.
Trends in pregnancy hospitalizations that included a stroke in the
United States from 1994 to 2007: reasons for concern? Stroke.
2011;42:2564–70. https://doi.org/10.1161/STROKEAHA.110.
610592.
11. Maski AM, Baijracharva S, Wenger J, Zhang D, Salahuddin S.
Epidemiology and mechanisms of de novo and persistent hyperten-
sion in the postpartum period. Circulation. 2015 November
3;132(18):1726–33. https://doi.org/10.1161/
CIRCULATIONAHA.
12. Kamel H, Navi BB, Sriram N, Hovsepian DA, Devereux RB,
Elkind MS Risk of a thrombotic event after the 6-week postpartum
period. N Engl J Med 2014;370:1307–1315. doi: https://doi.org/
10.1056/NEJMoa1311485.
13. Miller EC, Gatollari HJ, Too G, et al. Risk of pregnancy-associated
stroke across age groups in New York State. JAMA Neurol.
2016;73(12):1461–7. https://doi.org/10.1001/jamaneurol.2016.
3774.
14. Miller EC, Yaghi S, Boehme AK, Willey JZ, Elkind MS, Marshall
RS. Mechanisms and outcomes of stroke during pregnancy and the
postpartum period: a cross-sectional study. Neurol Clin Pract.
2016;6(1):29–39.
15. van Veen TR, Panerai RB, Haeri S, Griffioen AC, Zeeman GG,
Belfort MA. Cerebral autoregulation in normal pregnancy and pre-
eclampsia. Obstet Gynecol. 2013;122(5):1064–9.
16. Hammer ES, Cipolla MJ. Cerebrovascular dysfunction in pre-
eclamptic pregnancies. Curr Hypertens Rep. 2015;17(8):64.
17. Sanghavi M, Rutherford JD. Cardiovascular physiology of preg-
nancy. Circulation. 2014;130:1003–8.
18. Mahendru AA, Everett TR, Wilkinson IB, Lees CC, McEniery CM.
A longitudinal study of maternal cardiovascular function from pre-
conception to the postpartum period. J Hypertens. 2014;32:849–56.
19. Robson SC, Hunter S, Moore M, Dunlop W. Haemodynamic
changes during the puerperium: a Doppler and M-mode echocar-
diographic study. Br J Obstet Gynaecol. 1987;94:1028–39.
20. Hunter S, Robson SC. Adaptation of the maternal heart in pregnan-
cy. Br Heart J. 1992;68:540–3.
21. Cheung KL, Lafayette RA. Renal physiology of pregnancy. Adv
Chronic Kidney Dis. 2013;20:209–14.
22. Berkane N, Liere P, Oudinet JP, Hertig A, Lefèvre G, Pluchino N,
et al. From pregnancy to preeclampsia: a key role for estrogens.
Endocr Rev. 2017;38(2):123–44.
23. Conrad KP. Maternal vasodilation in pregnancy: the emerging role
of relaxin. Am J Phys Regul Integr Comp Phys. 2011;301(2):
R267–75.
24. . Kodogo V, Azibani F and Sliwa K. Role of pregnancy hormones
and hormonal interaction on the maternal cardiovascular system: a
literature review. Clin Res Cardiol. Epub ahead of print 26 February
2019. DOI: https://doi.org/10.1007/s00392-01901441-x
25. Conrad KP. Emerging role of relaxin in the maternal adaptations to
normal pregnancy: implications for preeclampsia. Semin Nephrol.
2011;31:15–32.
26. Fisher C, MacLean M, Morecroft I, Seed A, Johnston F, Hillier C,
et al. Is the pregnancy hormone relaxin also a vasodilator peptide
secreted by the heart? Circulation. 2002;106:292–5.
Page 9 of 11 58
27. O’sullivan KP, Marshall SA, Cullen S, Saunders T, Hannan NJ,
Senadheera SN, et al. Evidence of proteinuria, but no other charac-
teristics of pre-eclampsia, in relaxin-deficient mice. Reprod Fertil
Dev. 2017;29:1477–85. https://doi.org/10.1071/RD16056.
28. Marshall SA, Leo CH, Senadheera SN, Girling JE, Tare M, Parry
LJ. Relaxin deficiency attenuates pregnancy-induced adaptation of
the mesenteric artery to angiotensin II in mice. Am J Physiol Regul
Integr Comp. 2016a;310:R847–57. https://doi.org/10.1152/
ajpregu.00506.2015Physiol.
29. Mirabito Colafella KM, Samuel CS, Denton KM. Relaxin contrib-
utes to the regulation of arterial pressure in adult female mice. Clin
Sci. 2017;131:2795–805. https://doi.org/10.1042/CS20171225.
30. Gooi, J. H., Richardson, M. L., Jelinic, M., Girling, J. E., Wlodek,
M. E., Tare, M., et al. (2013). Enhanced uterine artery stiffness in
aged pregnant relaxin mutant mice is reversed with exogenous re-
laxin treatment. 89:18. Biol. Reprod doi: https://doi.org/10.1095/
biolreprod.113.108118.
31. Mirabito Colafella KM, Samuel CS, Denton KM. Relaxin contrib-
utes to the regulation of arterial pressure in adult female mice. Clin
Sci. 2017;131:2795–805. https://doi.org/10.1042/CS20171225.
32. Lumbers ER, Pringle KG. Roles of the circulating renin
angiotensin- aldosterone system in human pregnancy. Am J Phys
Regul Integr Comp Phys. 2014;306(2):R91–R101.
33. August P, Lindheimer MD. Pathophysiology of preeclampsia.
Hypertension. 1995;142:2407–26.
34. Chesley LC. Hypertensive disorders in pregnancy. New York:
Appleton-Century-Crofts; 1978.
35. Lindheimer MD, Katz AI. Renal physiology and disease in preg-
nancy. In: Seldin DW, Giebisch G, editors. The kidney: physiology
and pathophysiology. 2nd ed. New York: Raven Press; 1992. p.
3371–431.
36. Granger JP, Alexander BT, Bennett WA, et al. Pathophysiology of
pregnancy-induced hypertension. Am J Hypertens. 2001;14:178S–
85S.
37. R e d m a n C W , S t a f f A C . P r e e c l a m p s i a , b i o m a rk e rs ,
syncytiotrophoblast stress, and placental capacity. Am J Obstet
Gynecol. 2015;213(4 Suppl):S9.e1–S9–S11.
38. Maloney KF, Heller D, Baergen RN. Types of maternal hyperten-
sive disease and their association with pathologic lesions and clin-
ical factors. Fetal Pediatr Pathol. 2012;31:319–23.
39. Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M,
Zeisler H, et al. The sFlt-1/PlGF ratio in different types of hyper-
tensive pregnancy disorders and its prognostic potential in pre-
eclamptic patients. Am J Obstet Gynecol. 2012;206:58–e1–8.
40. Ghuman N, Rhiener J, Tendler BE, White WB. Hypertension in the
postpartum woman: clinical update for the hypertension specialist. J
Clin Hypertens (Greenwich). 2009;11:726–33.
41. Makris A, Thornton C, Hennessy A. Postpartum hypertension and
nonsteroidal analgesia. Am J Obstet Gynecol. 2004;190:577–8.
42. Makkonen N, Harju M, Kirkinen P. Postpartum recovery after se-
vere pre-eclampsia and HELLP-syndrome. J Perinat Med. 1996;24:
641–9.
43. Berks D, Steegers EA, Molas M, Visser W. Resolution of hyper-
tension and proteinuria after preeclampsia. Obstet Gynecol.
2009;114:1307–14.
44. Suzuki H, Watanabe Y, Arima H, Kobayashi K, Ohno Y, Kanno Y.
Short- and long-term prognosis of blood pressure and kidney dis-
ease in women with a past history of preeclampsia. Clin Exp
Nephrol. 2008;12:102–9.
45. Walters BNJ, Thompson ME, Lee A, de Swiet M. Blood pressure in
the puerperium. Clin Sci (Colch). 1986;71:589–94.
46. Ferrazzani S, De Carolis S, Pomini F, Testa AC, Mastromarino C,
Caruso A. The duration of hypertension in the puerperium of pre-
eclamptic women: relationship with renal impairment and week of
delivery. Am J Obstet Gynecol. 1994;17:506–12.
 58 Page 10 of 11
47. Clark SL, Belfort MA, Dildy GA, et al. Emergency department use
during the postpartum period: implications for current management
of the puerperium. Am J Obstet Gynecol. 2010;203:38–e1–6.
48. Matthys LA, Coppage KH, Lambers DS, Barton JR, Sibai BM.
Delayed postpartum pre- eclampsia: an experience of 151 cases.
Am J Obstet Gynecol. 2004;190:1464–6.
49. Hargood JL, Brown MA. Pregnancy-induced hypertension: recur-
rence rate in second pregnancies. Med J Aust. 1991;154:376–7.
50. Noori M, Donald AE, Angelakopoulou A, Hingorani AD, Williams
DJ. Prospective study of placental angiogenic factors and maternal
vascular function before and after preeclampsia and gestational hy-
pertension. Circulation. 2010;122:478–87.
51. Silver HM, Seebeck M, Carlson R. Comparison of total blood vol-
ume in normal, preeclamptic, and nonproteinuric gestational hyper-
tensive pregnancy by simultaneous measurement of red blood cell
and plasma volumes. Am J Obstet Gynecol. 1998;179:87–93.
52. Ohashi Y, Ibrahim H, Furtado L, Kingdom J, Carvalho JC. Non-
invasive hemodynamic assessment of non-pregnant, healthy preg-
nant and preeclamptic women using bioreactance. [corrected]. Rev
Bras Anestesiol. 2010;60:603–13 335–40.
53. Ditisheim A, Wuerzner G, Ponte B, Vial Y, Irion O, Burnier M,
et al. Prevalence of hypertensive phenotypes after preeclampsia: a
prospective cohort study. Hypertension. 2018;71:103–9.
54. Martillotti G, Ditisheim A, Burnier M, Wagner G, Boulvain M,
Irion O, et al. Increased salt sensitivity of ambulatory blood pressure
in women with a history of severe preeclampsia. Hypertension.
2013;62:802–8. https://doi.org/10.1161/HYPERTENSIONAHA.
113.01916.
55. Weinberger MH, Fineberg NS, Fineberg SE, Weinberger M. Salt
sensitivity, pulse pressure, and death in normal and hypertensive
humans. Hypertension. 2001;37(2 pt 2):429–32.
56. Morimoto A, Uzu T, Fujii T, Nishimura M, Kuroda S, Nakamura S,
et al. Sodium sensitivity and cardiovascular events in patients with
essential hypertension. Lancet. 1997;350:1734–7. https://doi.org/
10.1016/S0140-6736(97)05189-1.
57. Fujii T, Uzu T, Nishimura M, Takeji M, Kuroda S, Nakamura S,
et al. Circadian rhythm of natriuresis is disturbed in nondipper type
of essential hypertension. Am J Kidney Dis. 1999;33:29–35.
58. Benschop L, Duvekot JJ, Versmissen J, van Broekhoven V,
Steegers E, Roeters van Lennep J Blood pressure profile 1 year
after severe preeclampsia. Hypertension. 2018 Mar;71(3):491–
498. doi: https://doi.org/10.1161/HYPERTENSIONAHA.117.
10338.
59. Reiter L, Brown MA, Whitworth JA. Hypertension in pregnancy:
the incidence of underlying renal disease and essential hyperten-
sion. Am J Kidney Dis. 1994;24:883–7.
60. Tan L-K, De Swiet M. The management of postpartum hyperten-
sion. BJOG Int J Obstet Gynaecol. 2002;109:733–6. https://doi.org/
10.1111/j.1471-0528.2002.01012.x.
61. Stagnaro-Green A. Postpartum thyroiditis. J Clin Endocrinol
Metab. 2002;87:4042–7.
62. Wuytack F, Smith V, Cleary BJ. Oral non-steroidal anti-inflamma-
tory drugs (single dose) for perineal pain in the early postpartum
period. The Cochrane Database of Systematic Reviews 2016, Issue
7. Art. No.:CD011352.
63. Snowden S, Nelson R. The effects of nonsteroidal anti-
inflammatory drugs on blood pressure in hypertensive patients.
Cardiol Rev. 2011;19:184–91.
64. Johnson AG, Nguen TV, Day RO. Do nonsteroidal anti-
inflammatory drugs affect blood pressure? A meta-analysis. Ann
Intern Med. 1994;121:289–300.
65. Narumiya S, Sugimoto Y, Ushikubi F. Prostanoid receptors: struc-
tures, properties, and functions. Physiol Rev. 1999;79:1193–226.
66. Palmer BF. Renal complications associated with use of nonsteroidal
anti-inflammatory agents. J Investig Med. 1995;43:516–33.
Curr Hypertens Rep (2020) 22:58
67. Executive summary: hypertension in pregnancy. American College
of Obstreticians and Gynecologists. Obstet Gynecol 2013;122:
1122–1131, Hypertension in Pregnancy.
68. Oscar A, Viteri MD, Joey A, England MD, Mesk A, Alrais MD,
et al. Association of nonsteroidal antiinflammatory drugs and post-
partum hypertension in women with preeclampsia with severe
fatures. Obstet Gynecol. 2017;130(4):830–5.
69. Blue NR, Murray-Krezan C, Drake-Lavelle S, Weinberg D,
Holbrook BD, Katukuri VR, et al. Effect of ibuprofen vs acetamin-
ophen on postpartum hypertension in preeclampsia with severe
features: a double-masked, randomized controlled trial. Am J
Obstet Gynecol. 2018;218(6):616–e1–616.e8.
70. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Preeclampsia
and risk of cardiovascular disease and cancer in later life: systematic
review and meta-analysis. BMJ. 2007;335:974.
71. Felder RA, White MJ, Williams SM, Jose PA. Diagnostic tools for
hypertension and salt sensitivity testing. Curr Opin Nephrol
Hypertens. 2013;22:65–76.
72. Schulman IH, Aranda P, Raij L, Veronesi M, Aranda FJ, Martin R.
Surgical menopause increases salt sensitivity of blood pressure.
Hypertension. 2006;47:1168–74.
73. Vikse B, Irgens L, Leivestad T, Skjaerven R, Iversen B. Pre-
eclampsia and the risk of end-stage kidney disease. N Engl J
Med. 2008;359:800–9.
74. Saxena AR, Karumanchi SA, Brown NJ, Royle CM, McElrath TF,
Seely EW. Increased sensitivity to angiotensin II is present postpar-
tum in women with a history of hypertensive pregnancy.
Hypertension. 2010;55:1239–45.
75. Khalil AA, Tsikas D, Akolekar R, Jordan J, Nicolaides KH.
Asymmetric dimethylarginine, arginine and homoarginine at 11-
13 weeks’ gestation and preeclampsia: a case-control study. J
Hum Hypertens. 2013;27:38–43.
76. Walters BNJ, Thompson ME, Lee A, de Swiet M. Blood pressure in
the puerperium. Clin Sci. 1986;71:589–94.
77. Därr R, Lenders JW, Hofbauer LC, Naumann B, Bornstein SR,
Eisenhofer G. Pheochromocytoma - update on disease manage-
ment. Ther Adv Endocrinol Metab. 2012;3(1):11–26. https://doi.
org/10.1177/2042018812437356.
78. Webster J, Koch HF. Aspects of tolerability of centrally acting
antihypertensive drugs. J Cardiovasc Pharmacol. 1996;27(Suppl):
S49–54.
79. Kelsey, Julie J.. “Drug principles in lactation.” (2016).
80. American Academy of Pediatrics Committee on Drugs. The trans-
fer of drugs and other chemicals into human milk. Pediatrics.
2001;108:776–89.
81. Magee LA, Miremadi S, Li J, Cheng C, Ensom M, Carleton B, et al.
Therapy with both magnesium sulfate and nifedipine does not in-
crease the risk of serious magnesium-related maternal side effects in
women with preeclampsia. Am J Obstet Gynecol. 193(1):153–63.
82. O’Donnell MJ, Yusuf S, Mente A, Gao P, Mann JF, Teo K, et al.
Urinary sodium and potassium excretion and risk of cardiovascular
events. JAMA. 2011;306:2229–38.
83. Burnier M, Phan O, Wang Q. High salt intake: a cause of blood
pressure-independent left ventricular hypertrophy? Nephrol Dial
Transplant. 2007;22:2426–9.
84. Aoki H, Ito N, Kaniwa N, Saito Y, Wada Y, Nakajima K, et al. Low
levels of amlodipine in breast milk and plasma. Breastfeed Med.
2018 Nov;13(9):622–6. https://doi.org/10.1089/bfm.2018.0158
Epub 2018 Sep 28.
85. Liedholm H, Melander A, Bitzen PO, Lonnerholm G, Mattiasson I,
Wilsson B, et al. Accumulation of atenolol and metoprolol in hu-
man breast. Milk.Eur J Clin Pharmacol. 1981;20:229–31.
86. Shannon ME, Malecha SE, Cha AJ. Angiotensin converting en-
zyme inhibitors (ACEIs) and angiotensin II receptor blockers
(ARBs) and lactation: an update. J Hum Lact. 2000;16:152–5.
Curr Hypertens Rep (2020) 22:58
87. Healy M. Suppressing lactation with oral diuretics. Lancet.
1961;277:1353–4.
88. Vigil-de Gracia P, Ruiz E, Lσpez JC, et al. Management of severe
hypertension in the postpartum period with intravenous hydralazine
or labetalol: a randomized clinical trial. Hypertens Preg nancy.
2007;26:163–71.
89. Vermillion ST, Scardo JA, Newman RB, Chauhan SP Chauhan
SP.A randomized, double-blind trial of oral nifedipine and intrave-
nous labetalol in hypertensive emergencies of pregnancy. Am J
Obstet Gynecol 1999;181:858–861.
90. Raheem IA, Saaid R, Omar SZ, Tan PC. Oral nifedipine versus
intravenous labetalol for acute blood pressure control in hyperten-
sive emergencies of pregnancy: a randomised trial. BJOG.
2012;119:78–85.
91. Sharma KJ, Greene N, Kilpatrick SJ. Oral labetalol compared to
oral nifedipine for postpartum hypertension: a randomized
Page 11 of 11 58
controlled trial. Hypertension in Pregnancy. 2017;36(1):44–7.
https://doi.org/10.1080/10641955.2016.1231317.
92. Vigil-de Gracia P, Ludmir J. The use of magnesium sulfate for
women with severe preeclampsia or eclampsia diagnosed during
the postpartum period. J Matern Fetal Neonatal Med. 2015;28:
2207–9.
93. Vigil-De Gracia P, Ramirez R, Durán Y, Quintero A. Magnesium
sulfate for 6 vs 24 hours post delivery in patients who received
magnesium sulfate for less than 8 hours before birth: a randomized
clinical trial. BMC Pregnancy Childbirth. 2017;17(1):241.
Published 2017 Jul 24. doi:https://doi.org/10.1186/s12884-017-
1424-3
Publisher’s Note Springer Nature remains neutral with regard to jurisdic-
tional claims in published maps and institutional affiliations.