Introduction
Hypertensive disorders occur in 2 to 8% of pregnancies,[1] and are a major cause of maternal morbidity and mortality, accounting for 25.7%
of maternal deaths in Latin America.[2] In Brazil, preeclampsia is the leading cause of severe maternal morbidity, and its
primary complication, eclampsia, is the most prevalent cause of maternal death.[3] Preeclampsia can present with various conditions ranging from mild forms of hypertension,
sometimes with no need for antihypertensive drugs, to severe forms with possible serious
complications, which require intensive care.[4]
Gestational hypertension is defined as the occurrence of systolic blood pressure levels > 140 mm
Hg or diastolic blood pressure > 90 mm Hg.[5] Preeclampsia is traditionally diagnosed when, associated with gestational hypertension
at a gestational age ≥ 20 weeks, significant proteinuria appears (≥ 0.3 g in a 24-hour
urine test), or there is end organ damage: renal (serum creatinine > 1.1 mg/dL), hepatic
(transaminases > 70 U/L, bilirubin > 1.2 mg/dL), cerebral (headache, seizures, posterior
reversible encephalopathy syndrome [PRES]), hematologic (thrombocytopenia < 100,000/mm3 or lactic dehydrogenase ≥ 600 U/L), or pulmonary (pulmonary edema, dyspnea not attributable
to another cause).[6]
Although it has been recognized as a disease for over one hundred years, the pathophysiology
of preeclampsia is not yet fully understood.[7] Previous studies have demonstrated histopathological differences between placentas
of healthy women and those of women with preeclampsia,[8] and, for several decades, it has been understood that the disease is mediated by
endothelial dysfunction due to placental malperfusion.[9] The hypothetical “two-stage” model suggests that a poorly perfused placenta (stage
1: without clinical symptoms) due to inadequate uterine spiral artery remodeling releases
antiangiogenic factors into the circulation (stage 2), and this determines the clinical
manifestation of preeclampsia.[10] Delivery, and consequent removal of the placenta, is the only effective treatment.[7]
Modern obstetric practices recommend taking maternal and fetal conditions into account
in maternal-fetal care, to ensure the safe monitoring of the pregnancies and achieve
the best outcomes for both mothers and newborns. Preeclampsia, a disease with a high
association with morbidity and mortality,[3]
[11] is a classic example of this dichotomous situation, in which it is sometimes necessary
to postpone the delivery to protect maternal health.[12] Approximately 13% of cases of preeclampsia develop before 34 weeks of gestation,
and 32% develop between 34 and 37 weeks,[13] and are associated with high risk of maternal complications,[14] as well as a high rate of medically-indicated premature births.[15]
[16]
[17]
While immediate delivery in cases of preeclampsia at over 37 weeks of gestation improves
the maternal and perinatal outcomes,[18]
[19] the scientific evidence is still inconclusive regarding the best timing of delivery
in the event preterm preeclampsia is diagnosed, due to complications related to prematurity.
The goal of the expectant management is to reduce the impact of medically-indicated
premature births. However, maternal and fetal surveillance is necessary, and the presence
of any serious signs should lead to delivery regardless of the gestational age.[18]
[19]
The objective of this review is to provide an update on the available evidence on
the best timing of delivery once preterm preeclampsia has been diagnosed.
Methods
A systematic literature review was performed to investigate the best timing of delivery
for women who develop preeclampsia before a gestational age of 37 weeks. The review
considered 3 years, from January 2014 to February 2017, and we used the PubMed database.
The Medical Subject Headings selected were preeclampsia, parturition and timing of delivery, combined in the following way: preeclampsia AND (parturition OR timing of delivery). Observational studies and clinical trials were included; systematic reviews, guidelines
and meta-analyses were excluded. The search was limited to studies published in English
or Portuguese.
The research protocol for this review was created in accordance with the patient,
intervention, comparison and outcome (PICO) strategy.[20] For the research protocol, the “patients” were defined as women who developed preeclampsia
before 37 weeks of gestation; “intervention” was defined as delivery within 24 hours
of the diagnosis of preeclampsia; a “comparison” was made in relation to the expectant
management; and the “outcomes” considered were the maternal (progression to severe
preeclampsia, eclampsia, hemolysis, elevated liver enzyme levels, and low platelet
levels (HELLP) syndrome, other serious maternal morbidities, or maternal death) and
fetal (prenatal death, admission to an intensive care unit [ICU], or respiratory disorders)
outcomes. The current study followed all recommendations of the Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement.[21]
The search identified a total of 629 studies. After an analysis of the titles by 2
independent reviewers, 78 articles were selected. After carefully reading the abstracts
of these articles, 16 were selected to be fully read and, afterwards, 6 were included
in the analysis of this review, 4 of which were observational studies,[13]
[14]
[22]
[23] and 2, clinical trials[24]
[25] ([Fig. 1]).
Fig. 1 Flowchart for the selection of articles for the systematic review.
A brief description of each of the studies included is presented in [Table 1]. The results are shown according to the gestational age of preeclampsia onset (before
34 weeks and between 34 and 37 weeks).
Table 1
Studies included in this systematic review, with presentation of the type of study,
number of participants and main findings
|
Authors, year, country
|
Type of study
|
Partic.
|
Main findings
|
|
Owens et al, 2014, USA[25]
|
RCT
|
183
|
Expectant management: 75 cases; immediate delivery: 94 cases.
Progression to severe preeclampsia: 41% versus 3% (expectant management versus immediate
delivery: significant difference).
Most common diagnostic criterion of severe preeclampsia: severe hypertension (> 160 × 110 mm
Hg).
Newborn with weight below the 10th percentile: 15% versus 20% (expectant management
versus immediate delivery: no significant difference).
Admission to neonatal ICU: 19% versus 21% (expectant management versus immediate delivery:
no significant difference).
Respiratory distress syndrome: 8% versus 12% (expectant management versus immediate
delivery: no significant difference).
|
|
Broekhuijsen et al, 2015, Holland[24]
|
RCT
|
703
|
Expectant management: 351 cases; immediate delivery: 352 cases.
Occurrence of maternal complications: 3.1% versus 1.1% (expectant management versus
immediate delivery: no significant difference).
HELLP syndrome: 2% versus 1% (expectant management versus immediate delivery: no significant
difference).
Occurrence of perinatal complications: 1.7% versus 5.7% (expectant management versus
immediate delivery: significant difference; relative risk: 3.3).
Admission to neonatal ICU: 3.7% versus 7.4% (expectant management versus immediate
delivery: significant difference; relative risk: 2.0).
Transient tachypnea: 1.7% versus 5.7% (expectant management versus immediate delivery:
significant difference; relative risk: 3.3).
|
|
Lisonkova et al., 2014, USA[14]
|
RO
|
670,120
|
Increased incidence of preeclampsia in the studied period (2000 to 2008), from 2.9%
to 3.1%. Early-onset preeclampsia = 0.3%, and late-onset = 2.7%, with a 4.5% increase
in the incidence of early-onset preeclampsia.
The maternal mortality rate[b] among women with early-onset preeclampsia was 4 times higher than for those with
with late-onset (42.1 versus 11.2).
Severe maternal morbidity[c] was higher among women with early-onset preeclampsia (12.2 versus 5.5).
Increased risk of cardiovascular, respiratory, neurological, kidney and liver complications
among women with early-onset compared with late-onset preeclampsia.
|
|
Pettit et al, 2015, Australia[13]
|
RO
|
696
|
Early; late; term.
Incidence: 13%; 32%; 55%.
Cesarean section rate: 70%; 55%; 44%.
Severe hypertension: 43%; 35%; 31%.
Fetal growth restriction: 32%; 18%; 15%.
Perinatal mortality:[a] 80, 10, 5
|
|
Helou et al, 2016, Australia[22]
|
RO
|
516
|
Incidence of preeclampsia: 3.5%.
Mean gestational age at delivery among women with preeclampsia: 36 weeks.
Fetal growth restriction: 21.7%
Admission to neonatal ICU: 28.5%
In 77% of the cases of late-onset preeclampsia, the women underwent expectant management,
with progression to severe preeclampsia in 5.2% of the cases.
|
|
McKinney et al, 2016, USA[23]
|
RO
|
199
|
Incidence of fetal growth restriction in women with late-onset preeclampsia: 31%.
Progression to severe preeclampsia: 51.1% (among normal fetuses) and 42.9% (among
fetuses with growth restriction).
The interval to delivery was significantly shorter in women with fetal growth restriction
(median [interquartile range] of 3 [1.6] days versus normal growth, 5 [2.12] days;
p < 0.001).
|
Abbreviations: HELLP, hemolysis, elevated liver enzyme levels, and low platelet levels;
ICU, intensive care unit; Partic., number of participants; RCT, randomized clinical
trial; RO, retrospective observational.
Notes: aPer thousand births;
b per group of 100,000 births;
c for any severe maternal morbidity, per group of 100 births.
Results
Preeclampsia Onset Prior to 34 Weeks
The observational studies showed that women with early-onset preeclampsia had more
severe conditions upon developing the disease,[13] and were more frequently subject to serious maternal morbidities such as renal failure,
sepsis, the need for a hysterectomy or blood transfusion, and increased risk of maternal
death,[14] with higher cesarean rates (70%).[13] When preeclampsia was diagnosed before 30 weeks, there was an association with fetal
growth restriction (FGR), and the interval to delivery was shorter.[23] Progression to severe preeclampsia occurred in almost half (43%) of the women under
expectant management.[13]
On perinatal outcomes, the observational studies presented a high incidence of FGR,[14] leading to lower birth weights among women with preeclampsia; almost 1/3 (32%) were
below the 10th percentile in weight for their gestational age. There was also a high
rate of perinatal mortality (80/1,000 live births).[13]
Onset of Preeclampsia between 34 and 37 Weeks
Among the women who developed preeclampsia between 34 and 37 weeks, the results of
the observational studies had a wide range of findings: the progression to severe
forms of the disease was as high as 51% and 35%[13]
[23] in 2 of the considered studies, and as low as 5% in the other.[22] The association with the risk of complications, even though significantly lower
when compared with the women with early-onset preeclampsia, was only observed in one
of the studies evaluated.[14] Among the clinical trials, one of them, with 703 women, showed that the option of
expectant management added 5 to 10 days to the gestation, with no significant increase
in maternal complications, such as HELLP syndrome, thromboembolic events, placental
abruption, eclampsia and maternal death.[24] Another study involving 169 women found a significant difference in the progression
to other severe forms of the disease among women under expectant management (41% versus
3%).[25]
Considering the perinatal outcomes, one of the observational studies identified significant
weight gain at birth in the comparison between expectant management and immediate
delivery, as well as a lower need for ICU admission and decreased risk of perinatal
death.[13] One of the clinical trials indicated similar perinatal outcomes in the two groups,[25] while another showed an increased risk of significant neonatal complications for
newborns who were delivered immediately compared with cases in which expectant management
was adopted.[24]
Discussion
Women with preterm preeclampsia had a greater risk of medically-indicated premature
birth; however, if there were no signs of severe maternal complications or impaired
fetal well-being during close surveillance, delaying delivery when preeclampsia is
diagnosed before 37 weeks (and especially in cases of early-onset preeclampsia) improved
the neonatal outcomes, without major harm to the maternal health.
Previous systematic reviews with a similar scope and different temporal profiles have
confirmed the low number of clinical trials that compare expectant management and
immediate delivery in relation to the maternal and perinatal outcomes of preterm preeclampsia.[26]
[27] Conducting clinical trials for diseases with high morbidity and mortality and low
frequency, as is the case of early-onset preeclampsia, can be challenging, due to
the difficulties in implementing inclusion protocols and carrying out the studies,
in addition to the ethical issues involved. In this context, it is important to consider
the need for further studies, preferably multicenter ones, including various high
and low-income settings.
Expectant management is possible for cases of preeclampsia when the gestational age
at diagnosis is < 37 weeks, and the major goal is improving perinatal outcomes, especially
reducing neonatal complications; however, the management should be reevaluated if
there are signs of progression to severe forms of preeclampsia, or if there is evidence
of impaired fetal well-being ([Table 2]). The occurrence of severe preeclampsia is diagnosed in the presence of any of the
following criteria: systolic blood pressure ≥ 160 mm Hg; diastolic blood pressure
≥ 110 mm Hg, with no response to treatment after 4 hours; eclampsia (seizures); and
persistence, worsening or association of laboratory markers, such as platelet counts < 100,000/mm3, aspartate transaminase (AST) > 70 U/L, and creatinine > 1.1 mg/dL. Fetal growth
restriction, oligohydramnios, changes in the umbilical artery observed by Doppler
assessment, and non-reassuring cardiotocography are indications of impaired fetal
well-being, and demand surveillance. Clinical symptoms such as pulmonary edema and
right hypochondrium pain not attributable to other causes, or brain disorders, such
as headaches, and visual disorders (scotomas, obnubilation) are also considered reasons
for interrupting the expectant management. In the absence of such clinical signs or
laboratory or ultrasound findings, the delivery should reach term (37 weeks).[18]
Table 2
How to talk with pregnant mothers and their families about the risks, benefits and
uncertainties of immediate delivery versus expectant management when preterm preeclampsia
is diagnosed (adapted from Chappell, Milne e Shennan, 2015)[18]
|
• Explain what is happening with her and her baby; clarify that she is not guilty
of the occurrence of preeclampsia, which can happen to anyone. Explain that the team
is available to answer her questions. Go over the symptoms that she must immediately
report: headache, vomiting, abdominal pain, changes in vision such as blurred vision
or flashes, sweating of the face, feet or hands, and reduced fetal movement.
• Explain why she is being hospitalized and the importance of staying, to improve
outcomes in case of emergency.
• Inform her that preeclampsia is generally resolved with delivery and removal of
the placenta. Say that as long as it is receiving nutrients, the best place for the
baby is inside the mother, but if the situation changes, delivering the baby and receiving
neonatal care may be better.
• Explain the two possibilities: labor induction or cesarean section (if indicated)
in the next 24 hours, or remaining in the hospital until 37 weeks or before, if there
are any changes in her clinical condition. At 37 weeks, delivery is the best option.
|
Early-onset preeclampsia, before 34 weeks, occurs less frequently than the late-onset
(after 37 weeks) form of the disease, but it is associated with higher maternal morbidity
and mortality.[14] Early-onset preeclampsia is more frequently observed in women suffering from chronic
hypertension,[28] and is also more frequent among primiparous women and those with diabetes.[14] In women with previous hypertension, diagnosing preeclampsia can be challenging.
Therefore, initial screening for proteinuria, seeking any pregestational disease,
and knowledge of the initial blood pressure levels are important at the beginning
of the antenatal care.[28] Furthermore, women who develop early-onset preeclampsia are at a greater risk of
developing several serious complications, such as acute renal failure, respiratory
morbidities, cardiomyopathies, sepsis and a chance of maternal death nine times higher.[14]
Preeclampsia that develops between 34 and 37 weeks, also called preterm late-onset
preeclampsia, is more frequent than early-onset preeclampsia, but with reduced severity.[13]
[14] Women aged between 20 and 34 years are the most prone, as well as those with diabetes
and those with male fetuses.[14] Smoking is associated with a lower incidence of this condition in this gestational
age range.[14]
In countries with socioeconomic development similar to Brazil, hypertensive disorders
are the major reason for medically-indicated premature births, with increased rates
of cesarean section (c-section).[29] Nevertheless, clinical trials have shown that preterm labor induction, when indicated,
could reduce the occurrence of c-sections by ∼ 40%.[24]
[25] Therefore, when preeclampsia occurs, the route of delivery should preferably be
vaginal. Induced labor should be considered when there is maternal clinical stability,
good fetal well-being, a favorable cervix, and the gestational age is > 32 weeks.
A multidisciplinary approach is required, with the support of the anesthesia and neonatal
teams.[18]
The decision toward immediate delivery should not be mistaken with an emergency or
sudden delivery. It is important to establish that, when choosing immediate delivery,
the studies considered “immediate” a delivery within 24 hours, prioritizing the maternal
clinical condition, including the use of magnesium sulfate, intravenous antihypertensive
drugs, or corticosteroid therapy, when indicated, as well as a programmed transfer
to a center with maternal and neonatal ICUs.[18]
[24]
[25]
Current data support the idea that early-onset preeclampsia may be a more serious
condition than late-onset preeclampsia. However, when it is possible to delay the
timing of the delivery beyond 34 weeks, there is a considerable improvement in perinatal
outcomes. The study by Pettit et al, which had a significant number of cases (n = 696),[13] showed that the women who developed early-onset preeclampsia had a mean gestational
age at delivery of 33 weeks, compared with 38 weeks for late-onset (term preeclampsia),
with higher incidence of c-sections (70%) among women with early-onset preeclampsia.
The perinatal mortality rate in this group was 80/1,000, but dropped to 10/1,000 in
cases of preterm late-onset preeclampsia (between 34–37 weeks), and to 5/1,000 in
cases of term preeclampsia (≥ 37 weeks).
In cases of early-onset preeclampsia with FGR, it is essential that women be followed
in a hospital with the resources to monitor the fetal well-being, and that is also
equipped with a neonatal ICU. In such situations, the decision to transfer the patient
or to use corticoids for fetal lung maturity should not be delayed, since the interval
between diagnosis and delivery is usually very short, even among expectant management
cases.[23]
A systematic review with a meta-analysis of clinical studies conducted up to 2014
was published in 2017.[30] It showed that the maternal outcomes did not worsen, despite a significant difference
in the occurrence of placental abruption in women who underwent expectant management
after the diagnosis of early-onset preeclampsia. In terms of perinatal outcomes, the
mortality rate in both groups was similar; however, there was a higher occurrence
of complications, such as the need for ventilatory support, intraventricular hemorrhage
and hypoxic-ischemic encephalopathy among the newborns of women who underwent an elective
delivery before 34 weeks of gestation for severe preeclampsia compared with those
undergoing expectant management. The results highlight the importance of larger studies
to draw more definitive conclusions, especially considering the maternal outcomes.
A similar conclusion was also reached in the latest Cochrane review on the subject.[26]
To evaluate preeclampsia outcomes and the ideal timing of delivery for women between
the 34th and 37th weeks of gestation, a Dutch group conducted a major study (HYPITAT-II)[24] that included ∼ 700 women randomized into 2 groups: scheduled birth (labor induction
or c-section) within 24 hours of the diagnosis of preeclampsia, and expectant management
until 37 weeks of gestation. The women included in this study had been diagnosed with
gestational hypertension or preeclampsia, with no evidence of severe features, and
adequate fetal well-being. The maternal outcomes, including thromboembolic events,
pulmonary edema, HELLP syndrome, eclampsia, placental abruption and maternal death,
were similar between the two groups, with a mean period of seven days between diagnosis
and birth among the expectant management group. In terms of perinatal outcomes (Apgar
score < 7 at the 5th minute, cord blood acidosis, neonatal ICU admission, perinatal
death, neonatal infection, hypoglycemia, transient tachypnea, meconium aspiration
syndrome, pneumothorax, periventricular leukomalacia, intraventricular hemorrhage,
seizures, and necrotizing enterocolitis), there was a 3.3 times greater relative risk
among women who underwent immediate delivery in comparison to those who had the delivery
postponed. Thus, the authors established that there is no justification for immediate
delivery when there is no severe maternal or fetal condition, given the perinatal
complications resulting from prematurity.
An American study published in 2014[25] with a design similar to the Dutch study,[24] but with far fewer included cases (169), showed a progression to severe preeclampsia
in 41% of the women under expectant management, compared with only 3% of those who
underwent immediate delivery. Considering the perinatal outcomes, the birth weight
reduction was only around 300 g in the cases of immediate delivery, with no difference
in the other studied outcomes. Therefore, the authors suggested that the timing of
the delivery should be immediate, and that expectant management should only be considered
in selected cases. Nevertheless, the small number of women, associated with the single-center
nature of the study, is a weak point of the study that must be considered.
As in the American study,[25] the study that preceded the HYPITAT-II,[24] HYPITAT-I,[19] provided evidence that expectant management in cases of preeclampsia after 36 weeks
heightened the risk of occurrence of maternal complications, without improvement in
fetal outcomes. HYPITAT-II, which evaluated more women at more institutions, did not
confirm the findings of the initial study.
Two meta-analyses[27]
[30] published in 2017 demonstrated that immediate delivery, if preeclampsia is diagnosed
after 34 weeks, reduces the occurrence of maternal complications, including HELLP
syndrome. With respect to the perinatal outcomes, after 34 weeks, 1 meta-analyses[30] did not observe neonatal or fetal deaths in either group. However, it did not evaluate
the occurrence of various significant complications among the newborns. The other
meta-analysis[27] stated that there were large differences among the studies that were selected, which
did not enable further statistical evaluations, but the analysis showed a greater
occurrence of respiratory distress and need for admission to an ICU among newborns
whose birth occurred immediately after the diagnosis of preeclampsia compared with
those whose mothers were under expectant management.
According to various studies, it is prudent to consider admission to a hospital that
has intensive neonatal and adult care for women diagnosed with preeclampsia between
34 and 37 weeks, and close maternal and fetal surveillance, considering the risks
of progression of the disease. Referral centers should provide adequate training on
how to deal with severe cases, with special attention regarding how to provide adequate
guidance to the woman and her family, considering information about outcomes and follow-up,
sharing responsibility in the decision-making, especially between 34 and 37 weeks
of gestation. Awareness of the relevant symptoms that should be promptly communicated
to the care team is also key ([Table 2]).[18]
As far as the follow-up of the women who choose the expectant management, the recommendations
are blood pressure monitoring at least every six hours, and laboratorial tests every
two days or less, at the physician's discretion. The fetal well-being evaluation should
entail an ultrasound with Doppler velocimetry at the time of admission and then weekly,
or at shorter intervals, at the physician's discretion. A cardiotocography should
also be performed for fetal well-being assessment.[18]
The use of magnesium sulfate to prevent eclampsia has already been substantiated,
and recent meta-analyses have proven its role in reducing seizures and potentially
decreasing maternal mortality.[31] This effect has been confirmed in studies outside the controlled environments of
clinical trials, indicating that its use in the daily practice is associated with
a reduction in eclampsia cases.[32] Nevertheless, there are known obstacles to its use, such as difficulty obtaining
it in primary care facilities and lack of knowledge, or lack of well-established clinical
protocols for its use,[33] which impacts on its routine use to decrease preeclampsia complications.
More recently, studies showed that magnesium sulfate serves as a neuroprotective medication
for fetuses in cases of imminent premature birth, especially under 32 weeks, reducing
the occurrence of cerebral palsy.[34]
[35]
[36] No maternal complications associated with its use have been observed. The recommendation
is to administer a loading dose of 4 g, followed by 1 g every hour. The infusion of
magnesium sulfate, when used for fetal neuroprotection, should be stopped immediately
after birth.
The clinical use of biomarkers for risk prediction, preclinical diagnosis, and to
determine cases more prone to develop clinical complications is being extensively
studied, with important breakthroughs in the last decade due to a better understanding
of the pathophysiology of preeclampsia.[37] The role of angiogenic and antiangiogenic biomarkers is unfolding, and technologies
that enable their adequate and precise assessment are being developed, so that the
results will ensure the predictive, diagnostic and prognostic approaches.[38] The main biomarkers that have been studied are placental growth factor (PlGF), soluble
fms-like tyrosine kinase-1 (sFlt-1), and pregnancy-associated plasma protein A (PAPP-A).
All are highly sensitive in diagnosing early-onset preeclampsia, but demonstrate worse
results for identifying late-onset preeclampsia.[39] Many studies to determine the best timing and how to implement those tests in the
daily clinical practice are currently ongoing.[40]
[41]
[42] Future studies, and the association of biomarkers with ultrasound findings, promise
to improve the prediction of preeclampsia and its early management with measures that
can reduce the morbidity and mortality associated with the disease.[39]
Preeclampsia can be a devastating event for many women, but most survive and may choose
to become pregnant again. There is conflicting information in the literature regarding
the chance of preeclampsia recurring in future gestations. Individual studies have
shown that the occurrence of preeclampsia substantially increases the risk of recurrence
in later gestations and, in such cases, the disease can develop earlier, with more
severe complications.[43]
[44] However, a meta-analysis based on individual participant data (IPD) showed that
the rate of recurrence of preeclampsia was 21%, with this risk increasing if there
was HELLP syndrome or FGR in the previous gestation. The study found that, in the
event of recurrence, the forms of preeclampsia were less severe. However, it is relevant
to note that few of the considered studies were from low or middle income settings.[45] It is essential, therefore, that these women receive proper counseling considering
the risks, taking into account their personal medical history, and how the disease
manifested and progressed in the previous gestation. Among cases of severe early-onset
preeclampsia, other underlying conditions should also be investigated postpartum,
such as antiphospholipid syndrome, and interventions such as low dose aspirin and
calcium (in places of low dietary intake) should also be performed.[46]
In addition, women who have survived preeclampsia are at risk of developing cardiovascular
diseases in the long term. A literature review published in 2015 evaluating the risk
of acute myocardial infarction and strokes in women who had preeclampsia showed a
greater risk of such outcomes, as well as an increased risk of developing chronic
hypertension,[47] reinforcing that preeclampsia is a disease of endothelial dysfunction, which may
not be resolved at the end of pregnancy.[48] Therefore, the literature provides evidence that preeclampsia is a risk factor for
future cardiovascular disease, and that women who developed it should receive special
care, similar to that provided for other risk factors, such as hypertension, dyslipidemia,
obesity and smoking.[49] In the postpartum period, women with a history of preeclampsia should be informed
about the interventions that have an impact on such risk factors, such as physical
exercise and quitting smoking. If preeclampsia is understood as an endothelial disease,
it also implies increased risks of developing chronic kidney disease during life,
and this should also be assessed inj the postpartum period.[50]
[51]
The main recommendations found through this systematic review regarding the timing
of delivery in women with early-onset preeclampsia are presented in [Table 3], while the recommendations for those who developed preeclampsia between 34 and 37
weeks are presented in [Table 4].
Table 3
Timing of delivery recommendations for women diagnosed with preeclampsia before 34
weeks
|
• Early-onset preeclampsia is less frequent than late-onset preeclampsia, but is more
severe.
• It occurs more frequently in primiparas, and is associated with maternal comorbidities,
such as chronic hypertension and diabetes.
• The difference between uncontrolled chronic hypertension and superimposed preeclampsia
depends on early, adequate and quality antenatal care, with an investigation of the
complications associated with hypertension, which should be performed as soon as possible,
checking whether any target organs have been affected, such as: the kidneys (urea
dosage, creatinine and proteinuria) the heart (electrocardiogram, chest X-ray and
cardiological assessment, with other tests, if necessary) and the eyes (eye exam to
identify hypertensive retinopathy).
• Women with early-onset preeclampsia are more prone to serious complications during
pregnancy and the postpartum period, as well as to an increased risk of death.
• Early-onset preeclampsia is an important determining factor for medically-indicated
preterm birth, with increased perinatal mortality arising from this condition.
• The latency time between the diagnosis of early-onset preeclampsia and the timing
of the delivery is generally short (less than one week); therefore, measures such
as antenatal corticosteroid therapy for fetal lung maturity and transfer to hospital
units with more support (maternal and neonatal intensive care units) should not be
delayed.
• There is no definitive evidence in the literature on the best timing of delivery.
The decision upon expectant management should consider close maternal and fetal surveillance,
and if there is impaired maternal or fetal health, delivery should be performed, with
adequate measures for better clinical support, such as the use of magnesium sulfate
to prevent eclampsia.
|
Table 4
Timing of delivery recommendations for women diagnosed with preeclampsia between 34
and 37 weeks
|
• Although late-onset preeclampsia is more frequent, it is less serious than early-onset
preeclampsia, and generally affects younger women (aged between 21 and 34 years).
• Evidence suggests that expectant management is not associated with the development
of major maternal complications.
• Immediate delivery increases the risk of perinatal complications, especially those
associated with prematurity, but it does not increase neonatal mortality.
• The decision on the timing of delivery should be shared with the patient and her
family, and expectant management may be an option when there are no serious maternal
conditions or impaired fetal well-being.
• Women with late-onset preeclampsia should be treated in a hospital environment,
under strict clinical, laboratory and ultrasound surveillance.
• Clinical surveillance should be performed daily, with subsequent control of blood
pressure (at least every six hours); the symptoms of severity should be clearly explained
to the patient and immediately considered by the care team.
• The laboratory assessment should be serial (two times per week), or whenever the
patient's clinical condition or symptoms worsen, searching for renal function, hepatic
or hematological damages.
• The fetal well-being assessment should entail an ultrasound with Doppler velocimetry
and cardiotocography at the time of admission and at least weekly, or at shorter intervals,
depending on each case.
• Decompensated blood pressure, laboratory abnormalities (platelets < 100,000; aspartate
transaminase > 70 U/L; creatinine > 1.1 mg/dL), clinical symptoms (epigastric or right
hypochondrium pain, or neurological symptoms), or evidence of impaired fetal well-being
determine immediate delivery.
• At 37 weeks, delivery should be performed, with possible labor induction.
|
