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Hypertension in Pregnancy: Do We need a NewAlgorithm?
  JOHTN
MECHANISMS
Hypertension in Pregnancy: Do We need a New
Algorithm?
1Tiny Nair, 2Akash Nair
1Head, 2Student
1Department of Cardiology, PRS Hospital, ThiruvananthapuramKerala, India
2Department of Internal Medicine, Government T.D. MedicalCollege, Alappuzha, Kerala, India
Corresponding Author: Tiny Nair, Head, Department ofCardiology, PRS Hospital, Thiruvananthapuram, Kerala, India
e-mail: tinynair@gmail.com
 
ABSTRACT
Management of hypertension in pregnancy is a challenge,since the spectrum spreads from asymptomatic status tolife-threatening complications like eclampsia. The time-testedAmerican College of Obstetricians and Gynecologists (ACOG)classification fails to precisely prognosticate outcome of thiscomplicated spectrum. Detection and risk stratification hasundergone significant conceptual changes with the newerunderstanding of pathophysiology of this complex problem,mandating change in diagnostic algorithms. Introduction ofbiochemical high-risk markers like soluble fms-like tyrosinekinase 1 (sFlt-1):placental growth factor (PlGF) ratio has profoundlyimpacted risk stratification. A new four-question-basedalgorithm is suggested and its implications are discussed.
Keywords: Algorithm, Eclampsia, Hypertension, Preeclampsia,Pregnancy.
How to cite this article: Nair T, Nair A. Hypertension in Pregnancy:Do We need a New Algorithm? Hypertens J 2017;3(3):113-117.
Source of support: Nil
Conflict of interest: None
 
 

INTRODUCTION

Hypertension is the most common medical conditioncomplicating normal pregnancy.1,2 It can present with differentmanifestations at different time lines in pregnancy,and can culminate in serious maternal and perinatalmortality and morbidity. A team management approachcomprising obstetrician, cardiologist, and nephrologist isoften called for, especially in complicated and high-riskcases, keeping in mind the challenges of choosing drugsthat are safe in pregnancy and nursing. The sudden temporaltransition of a relatively "benign" chronic hypertensionin pregnancy to a life-threatening complication,like eclampsia, is often rapid and unpredictable, makingit "the mother of all challenges."

The physiology, etiology, consequences, classification,diagnosis, and treatment of hypertension in pregnancy are complicated, vague, and often controversial; knowledge inthis area is evolving constantly. The traditional algorithmshave blind spots and grey areas that need to be addressed,especially in the background of Indian scenario.
 
This review and discussion is intended to analyzethe present information, tweeze it, and suggest alternativeclassification and diagnostic algorithm suitable andpractically useful to the clinicians at the bedside in India.

CLASSIFICATION

The ACOG describes four major hypertensive disordersin pregnancy. This is a time-tested classification that isaccepted worldwide and is used by the clinicians in Indiatoo. They are as follows:
  • Chronic hypertension
  • Preeclampsia (PE)
  • Chronic hypertension with superimposed PE
  • Gestational hypertension

CHRONIC HYPERTENSION

It is defined as blood pressure (BP) 140/90 mm Hg or higherthat develops before 20 weeks of gestation. It is usually dueto essential hypertension. Even though chronic hypertensionin pregnancy is less ominous than PE, its prognosisbecomes unfavorable if the patients develop superimposedPE.1,3-6 Advanced maternal age and obesity are commonassociations of chronic hypertension in pregnancy. Epidemiologicaldata show that 3.6 to 9.1% of pregnancies arecomplicated by chronic hypertension.

PREECLAMPSIA

Preeclampsia is a systemic syndrome characterized bywidespread maternal endothelial dysfunction. It presentsas hypertension that develops in the latter half of pregnancy(after 20 weeks of gestation) along with proteinuria(classically greater than 300 mg per day).

Preeclampsia can present in the absence of proteinuria,wherein there has to be features of any one of thefollowing target organ damages (TODs).
  • Neurological symptoms-headache, visual blurring
  • Thrombocytopenia-platelet count < 100,000/cumm
  • Pulmonary edema
  • Elevated hepatic transaminases enzymes (also calledtransaminitis)
  • Renal insufficiency-elevated serum creatinine >1.1 mg/dL (Table 1).


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Table 1: Key features of PE
Hypertension in Pregnancy: Do We need a NewAlgorithm?

ECLAMPSIA

A severe and dreaded complication of PE is eclampsia,characterized by PE plus seizures (not attributable to anyother causes like metabolic or neurogenic).

The HELLP syndrome, which is an acronym forHemolysis, Elevated Liver enzymes and Low Plateletcount, has poor outcome. It complicates about 1 in 1,000pregnancies.3,6,7 Disseminated intravascular coagulationoccurs in 20% of women with HELLP syndrome, whilepulmonary edema is found in 6% cases. Up to 8% ofHELLP syndrome can occur immediately after delivery.Generalized activation of coagulation, fibrin cross-linkingin the small blood vessels, microangiopathic hemolyticanemia, and consumption of platelets form the basicpathophysiology of this syndrome.

GESTATIONAL HYPERTENSION

Gestational hypertension (incidence 6%) develops after20 weeks of pregnancy and is generally not associatedwith PE. It is said that around 25% of those diagnosedwith gestational hypertension tend to develop proteinuriaand overt features of PE. This makes diagnosis of gestationalhypertension, more often a retrospective one, beingconfirmed in the postpartum state.3

TRADITIONAL ALGORITHM

The traditional algorithm is based on the "timing" ofdetection of hypertension in pregnancy. Hypertensiondeveloping for the first time before 20 weeks is morelikely to be benign, while those after 20 weeks is morelikely to get complicated by proteinuria and eventuallydevelops PE (Flow Chart 1).6,8

So with the present algorithm, we ask two key questions(Table 2). One the timing, two, the presence of PE

TRADITIONAL "TWO-QUESTION"
ALGORITHM


Timing of onset is sometimes vague and complicated,especially in Indian context. In the Indian social scenario, the pregnant mother travels back to her parental homefor confinement and that results in a change of caregiversomewhere in mid-trimester. In a poorly networkedhealth system, it is often difficult to get hold of records ofBP to risk stratify, depending on time of onset of hypertension.Similarly, many women in rural backgroundmay present late, making diagnosis on a time-scale-basedalgorithm problematic.
 
Flow Chart 1: Traditional algorithm
Hypertension in Pregnancy: Do We need a NewAlgorithm?

Table 2: Two key questions
Hypertension in Pregnancy: Do We need a NewAlgorithm?

UNDERSTANDING THE PATHOPHYSIOLOGY

The systolic BP tends to remain mostly unchanged inpregnancy (slight reduction till mid-pregnancy), whilethe diastolic BP tends to progressively decline, reachingits lowest level between 20 and 24 weeks of gestation, presumablycaused by the effects of vasodilatory neurohormonesand placental arteriovenous shunts. This fall maybe exaggerated in the presence of "chronic hypertension"of pregnancy. So a "slightly" high BP around 20 weeks ofpregnancy might be important, and needs to be investigatedto rule out early warning signs of PE. The graviduterus in later part of pregnancy may cause compressionon the splanchnic vascular beds, alter venous return, andcause change of supine BP, mandating the need for BPrecording in left lateral decubitus in the pregnant mother.

Hypertension resulting from medical interaction(white coat hypertension) is estimated to be responsiblefor hypertension recorded during pregnancy inaround 32% of cases, before 20 weeks of pregnancy. Such"spurious"high BP recording needs to be differentiatedfrom genuine hypertension and not "overtreated" withdrugs. White coat hypertension do not predispose to PE.9
 
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Despite the fact that large majority of chronic hypertensionare primary, young women (as compared withelderly women) are more likely to suffer from "secondary"hypertensions, like renovascular obstruction, renalparenchymal disease, adrenal pathology (aldosteronism,Cushing's syndrome, or pheochromocytoma). Ruling outsuch secondary pathology in pregnancy is a challenge.During normal pregnancy there is increased levels ofaldosterone and renin (in contrast to increased aldosteroneand decreased renin in aldosteronism), makingdiagnosis more difficult.

RISK TO MOTHER AND FETUS

The hypertensive mother is more likely to undergocesarean section (in contrast to normal vaginal delivery),abruptio placentae leading to maternal hemorrhage,posterior reversible encephalopathy, and cerebral hemorrhage,in addition to other usual hypertensive targetorgan defects (retinopathy, hypertensive encephalopathy,nephropathy, and heart failure).1,10 Control of hypertensionhas not conclusively shown to prevent developmentof such maternal complications.

Apart from higher perinatal death, intrauterinegrowth retardation and an increased incidence of congenitalcardiac malformations are more common inpregnancy complicated by hypertension. Surprisingly,control of hypertension with antihypertensive drugs hasnot shown to reduce such complications.11

PROBLEMS OF PRESENT CLASSIFICATION
  • The present classification looks at the problem froma disease purview, but from a clinical angle. A ladypresenting with high BP at 20 weeks of pregnancymay be chronic hypertension (not detected duringfirst antenatal visit or may never have had a previousantenatal visit). This is not uncommon in India,because by social diktat, the pregnant lady travels backto her parental home at a later part of pregnancy. Herantenatal records may not exist, or may not be available.This makes the present classification impractical.
  • The most dreaded complication of hypertension inpregnancy is PE, but studies have shown that treatingmild or even moderate hypertension does notensure nonprogression to PE. The classification failsto prognosticate as to whether she will develop fetalor maternal complications.
  • Treating the high-risk subset, on the contrary, preventshypertensive end-organ damages. This underscoresthe importance of following a risk-based algorithmin deciding who would benefit from drug treatmentof hypertension, rather than the type of hypertensionbased on a diagnosis approach (onset < 20 weeks).
  • It is estimated that around 30% patients presentingfor the first time with high BP prior to 20 weeks ofpregnancy may have white coat hypertension.9 Thisunderscores the need for ambulatory blood pressuremonitoring (ABPM) or home BP monitoring to confirmthe diagnosis.
  • Once PE has been essentially ruled out, the nextstep is to decide the need for medical management,particularly antihypertensive drugs. Problem ofthe traditional algorithm of deciding and stratifyingdepending on the time of onset of hypertensiondoes not help in this regard. The high-risk charactersdescribed (Table 3) indicate clear-cut need for drugtherapy.1,3,12


 
A useful rule of thumb is that there is no substantialevidence that drug therapy in mild to moderate hypertensionalters maternal or fetal outcome, in the absence ofhigh-risk features as described earlier (Flow Chart 2).13,14

In the proposed algorithm, the diagnosis moves insteps:
Step 1. Ambulatory BP or home BP is used to confirmthe presence of hypertension, since one-third of thosedetected to have hypertension may be "white coat effect."
Step 2. Features of PE are checked.
Step 3. Presence of high-risk features is looked for.This identifies those who need aggressive treatment, incontrast to those who do not.

Table 3: High-risk features
Hypertension in Pregnancy: Do We need a NewAlgorithm?

Flow Chart 2: New algorithm
Hypertension in Pregnancy: Do We need a NewAlgorithm?
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Hypertension in Pregnancy: Do We need a NewAlgorithm?
Fig. 1:Fetoplacental vasculature in normal pregnancy and PE


UNDERSTANDING PLACENTAL
ABNORMALITIES


During the course of normal pregnancy, the placentalcells tend to migrate up the uterine artery enabling itto remodel. This helps in hemodynamic preventionof vasoconstriction by a complex array of biochemicalcascade. Abnormality of trophoblastic penetrationleads to defective vasomotor function of spiral arteries,remodeling, and resultant ischemia. This results inalteration of cytokine levels, increase in endothelins,thromboxane A2, and reduction of nitric oxide andPlGF (Fig. 1).

The endothelium expresses a molecule called sFlt-1,which tend to combine with PlGF and neutralize it.During PE, the migration of the fetal cells to the uterine"spiral" artery is somehow impaired, leading to alteredvasoactive neurohormones, a reduction of PlGF andincrease of sFlt-1. Such biochemistry alteration remainedin the area of research till recently. An elevation ofsFlt-1 and reduction of PlGF have been fairly consistentand conform to the disease progression. Alteration ofthe ratio of sFlt:PlGF showed promise in small studies(Table 4).15-17

A publication by Harald et al14 clearly showed thatsFlt-1:PlGF ratio in women in a developmental cohortclearly predicted development of PE. This was subsequentlyproved in a validation cohort in the same trial.Subsequently, development of a simple biochemicaltest measuring the sFlt-1:PlGF ratio changed the whole concept of preemptive diagnosis and risk prediction ofhypertensive population in pregnancy.
 
Table 4: Soluble fms tyrosine kinase 1
Hypertension in Pregnancy: Do We need a NewAlgorithm?

Table 5: Cut-off values of sFlt-1:PlGF ratio
Hypertension in Pregnancy: Do We need a NewAlgorithm?

The cut-off values are shown in Table 5.
The introduction of sFlt-1:PlGF ratio in the diagnosticalgorithm makes room for a new four-question algorithm,which we feel could be simple and appropriate (Table 6).
 
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Table 6: Four key questions
Hypertension in Pregnancy: Do We need a NewAlgorithm?

Table 7: Termination of pregnancy on detection of PE
Hypertension in Pregnancy: Do We need a NewAlgorithm?

TERMINATION OF PREGNANCY

Termination of pregnancy depends on the time at whichfeatures of PE are detected. Earlier, PE needs expectanttreatment, rest, BP control. Termination of pregnancy isconsidered necessary in case of maternal or fetal distress.

In contrast, closer to 37 weeks, expectant managementis followed by planned delivery at 37 weeks7 (Table 7).

CONCLUSION

Managing hypertension in pregnancy is a challenge.The present algorithm based on time of onset and detectionof hypertension and classifying it into gestationaland chronic variety fails in the bedside because of itspoor predictability of development of PE and futurecomplications. A risk-based algorithm may be betterfor the clinician. Introduction of point of care biochemicalrisk markers (sFlt-1:PlGF) promises to bring aboutsignificant change in diagnosis and risk assessment. Anew proposed simple four-question algorithm needsvalidation.

REFERENCES
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