Hypertensive Disorders in Pregnancy Milind R Shah
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PIH: The Challenge1

Milind R Shah
 
INTRODUCTION
Pre-eclampsia has been a recognized pathological entity since the time of Hippocrates and ancient Greeks.1 After the invention of sphygmomanometer in 1896, arterial hypertension during pregnancy was recognized as part of eclampsia or pregnancy toxaemia. Many disorders associated with pregnancy are toxaemic in nature but the term toxaemia is used to include pre-eclampsia, imminent eclampsia and eclamsia. Nowa-days this term is not used as triad of hypertension, proteinuria and oedema but can be present in some other disorders as well. On the other hand, there are many cases of hypertension without oedema or proteinuria but of much clinical significance.
Hypertensive disorders in pregnancy is one of the major causes of maternal and perinatal mortality and morbidity. It is one of the commonest medical disorders diagnosed by obstetricians in clinical practice.2 Approximately 1,00,000 women die worldwide per annum because of eclampsia.3 It is said that pre-eclampsia and eclampsia contribute to death of a woman every 3 minutes worldwide.4 Majority of these conditions are preventable. Good antenatal supervision followed by appropriate treatment will definitely help mother and baby for good outcome. It has been observed that though it has much significance for maternal health it is at backyard as compared to haemorrhagic complications of pregnancy.
 
CLASSIFICATION
Though there are many terminologies and classifications used for cases of pregnancy with hypertension, Williams classification5 appears most practical which is follows:
  1. Pregnancy-induced Hypertension
    1. Without proteinuria or oedema.
    2. With proteinuria or oedema (Pre-eclampsia)—mild or severe.
    3. Eclampsia.
  2. Chronic hypertension.
  3. Pregnancy-aggravated hypertension.2
Hypertension in pregnancy has many different aetiologies. Classification by International Society for the Study of Hypertension in Pregnancy (ISSHP) has considered all various types of hypertensive disorders clearly.6
 
ISSHP Classification
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Definitions of Hypertension and Proteinuria Used in ISSHP Classification
There are many other causes of hypertension which are covered in the following classification7 which are more of physician's interest.
  1. Pregnancy-induced hypertension (Pregnancy with superimposed hypertension).
  2. Pre-existing hypertension (Hypertension with superimposed pregnancy).3
  1. Essential (Idiopathic) hypertension.
  2. Renal hypertension due to renal artery stenosis, glomerulonephritis, pylonephritis, interstitial nephritis (analgesics, diabetes, gout), polycystic disease, tuberculosis, neoplasm and rare congenital lesions.
  3. Adrenal causes like phaeochromocytoma, Cushing's syndrome, primary hyperaldosteronism (Conn's syndrome).
  4. Connective tissue diseases like polyarteritis nodosa, systemic lupus erythematosus, scleroderma.
  5. Coarctation of aorta.
It is important to diagnose hypertension or PIH accurately. The blood pressure 140/90 or greater or there has been an increase of 30 mmHg systolic or 15 mmHg of diastolic over baseline values on at least two occasions 6 or more hours apart is gold standard. Korotkoff V is accurate for measurement of diastolic blood pressure as this corresponds more closely to the intra-arterial pressure and is the most reproducible endpoint in pregnancy.8 Though we say pre-eclampsia is a triad of hypertension, oedema and proteinuria, it is a common conclusion that these two parameters are variable. Oedema could be gestational oedema, which ameliorates after lying down. There are many studies, which have observed convulsions before onset of proteinuria. Oedema need to be nondependent and usually involves face and hands as against in gestational oedema, which appears more on feet. Proteinuria should be taken as worsening sign of hypertensive disease and there is direct proportion of proteinuria to maternal and perinatal mortality and morbidity.
 
INCIDENCE AND AETIOLOGY
Overall incidence of PIH is said to be 6 to 8 per cent9 but it varies a lot in different parts of world and also has many other factors associated with it.
  • Parity: More common in nullipara
  • Age: Extremes of age
  • Race: More in black women than white women
  • Familial tendency: There is familial predisposition
    Genetics: It is said that maternal genotype is responsible for conveying a susceptibility to developing pre-eclampsia.10
  • Antenatal care: It definitely has association. It helps locate many revealed cases at rural areas and as it is preventable, also reduces incidence in population receiving antenatal care.
  • Multiple pregnancy or hydatiform mole or fetal hydrops (Intra-abdominal mechanical factors)
  • Under-nutrition or over-nutrition, particularly dietic deficiencies of calcium, vitamin B and D or other minerals
  • Chronic vascular or renal diseases4
  • Diabetes
  • History of hypertensive disorder in previous pregnancy: 20 to 50 per cent women had recurrence in their subsequent pregnancies11
  • Immunological causes.
 
Early Diagnosis and Prevention
As symptoms appear late there are signs, which need to be carefully elicited by clinician or health care provider. It is possible to detect cases early if we observe standard schedule of antenatal examination that is monthly till seventh month, fortnightly afterwards and weekly in ninth month. Meticulous and accurate blood pressure recording and weight measurement would be of great help. Upward trend in diastolic pressure though in normal range could be clue for diagnosis or at least alarm for close vigilance.
Single elevated blood pressure needs to be confirmed, preferably average of 4–5 readings before it is used in management decisions.12 Similarly, care need to be taken while using automatic blood pressure recorders as diastolic blood pressure recorded on these machines could be several mm of Hg lower than normal.13 Similarly, proteinuria needs to be tested by heating urine in a test tube. Urine stick testing may overestimate presence of proteinuria. It is better to confirm by a 24 hours collection for quantification.14
Many substances have been tried for prevention. Many small trials reported significant reduction in the incidence of pre-eclampsia in high-risk populations. However, collaborative low dose aspirin study in pregnancy (CLASP),15 a large randomized study could not found reduction in incidence. Similarly, calcium is essential in the synthesis of nitric acid, a potent vasodilator believed to contribute to the maintenance of reduced vascular tone in pregnancy. Many small trials found benefit of calcium supplementation in prevention of pre-eclampsia, but large trial of Levin reported no benefit.16
 
Prediction of PIH
Predicting PIH and treating the condition early will no doubt reduce the maternal as well as perinatal mortality and morbidity. For this, various tests have been proposed. Following are some common tests used for prediction of PIH.
  1. Roll-over test: Gant et al observed an increase of more than 20 mm diastolic pressure when a woman as turned from left lateral to the supine position between 28 and 30 weeks of pregnancy. However, a high false-positive reporting and low reproducibility in the same woman makes this screening test of low reliability.
  2. Angiotensin II infusion test: This test indicates that the probability of developing hypertension is 90 per cent, if a response occurs with 5administration of less than 8 mg/kg body weight of angiotensin. The test is invasive, risky and takes several hours to perform. It also requires the supervision by the physician over a long period.
  3. Hand grip test: It represents sympathetic nervous system activity, which is not the reason for generalized vasoconstriction in PIH. A rise of 20 mm of Hg diastolic pressure is considered a positive test, and though more reliable than roll-over test it takes 30 minutes to be completed.
  4. Radioimmunoassay: Though it is possible to detect microalbuminuria by RIA, use of RIA is cumbersome, expensive and not feasible.
  5. Serum uric acid: Serum uric acid rises 4 weeks before the onset of PIH.
  6. Calcium/creatinine ratio (CCR): The urine is also considered a predictor test, with a lower calcium excretion in pre-eclampsia-toxaemia. It has a sensitivity of 70 per cent and specificity of 95 per cent. Calcium:creatinine ratio of less than 0.04 is significant.
  7. Maternal plasma endothelium I level: Maternal plasma endothelin I level in early pregnancy is predictive in 55 per cent cases.
  8. Doppler flow velocimetry: It is used to study the blood flow in the uterine artery, umbilical and middle cerebral artery. Criteria are systolic/diastolic velocity ratio (S/D), high resistance index (RI) and pulsatile index. These have a low predictive value, though these are useful to see the effects of PIH on the fetus, such as IUGR and poor biophysical profile.
  9. Ultrasonic scan with Doppler: USG in the second trimesters (29 weeks) shows bilateral notching of the uterine artery in a woman at a high risk of developing PIH in 80 per cent cases with false-positive rate of only 5 per cent at 24 weeks. Bilateral notching of the uterine artery in early pregnancy suggests impending PIH.17
  10. Fibronectin level: Raised fibronectic level 4 weeks before the onset of PIH as a predictive test requires a large prospective study.
  11. Beta human chorionic gonadotrophin and human placental lactogen.18
  12. Maternal serum inhibin A: It is observed that maternal serum inhibin A level rises at 14 weeks of pregnancy in women who eventually develop PIH.19
    Over 160 substances have been shown to be increased in women with pre-eclampsia but all these studies are conflicting.
 
MANAGEMENT
Aims in management are:
  1. Control of hypertension.
  2. Prevention of eclampsia.
  3. Prevention of accidental haemorrhage and DIC.
  4. Prevention of renal damage.6
  5. Maintenance of placental perfusion.
  6. Monitoring fetal growth and fetal well-being.
  7. Planning timely delivery.
 
Stepwise Management of Pregnancy Hypertension20
Therapeutic strategies need to be aimed at ameliorating the maternal response at the same time improving perinatal outcome.
It is necessary to follow this stepwise management protocol in cases of PIH.
 
Screening
  1. Screen women at risk or signs of hypertension in pregnancy.
  2. Monitor those at risk in antenatal day unit.
 
Before Delivery
  1. Regularly updated management protocols.
  2. Early involvement of senior medical staff.
  3. Stabilization with antihypertensive agents.
  4. Prophylactic steroid administration if the pregnancy is under 34 weeks.
  5. Consider the need of magnesium sulphate.
  6. Continuing monitoring for signs of disease progression.
  7. Delivery of baby on the best day, the best way and at the best place.
 
Holistic Management in Special Situations21
There is lot of discussion about whether treatment should be offered or not for the patients with mild to moderate hypertension. This is because we mainly rely on evidence-based medicine. But there are some situations need treatment though there is no sufficient evidence to offer or refuse the treatment. These are:
  1. Patients from under-resourced or rural areas: Here, health care delivery may not be up to mark or could be inadequate. Patients may not be able to avail proper antenatal services because of variety of reasons like lack of education, lack of transport, monetary constraints or inefficient infrastructure or services. Here, patients may not go for regular check-up or cannot understand significance of danger signs like headache.
  2. Patients with proteinuria: Here, we should try to understand marked lability of blood pressure. Blood pressure is variable and can fluctuate on a minute to minute basis.22 The arteriolar vasodilatation may improve organ perfusion where we know there is multiorgan hypoperfusion.
  3. Patients with chronic hypertension with target organ damage: Patients with renal damage, left ventricular dysfunction or diabetes with vascular involvement can get exacerbation of their damage by mild hypertension.237
  4. Patients with previous perinatal loss: Sibai said that patients with mild to moderate chronic hypertension are at low risk and does not affect rate of pre-eclamsia, abruptio placentae or preterm delivery though we discontinue therapy. But he stated further that if patient had previous perinatal loss the treatment needs to be continued as now patient belongs to high risk category.24, 25
  5. Informed choice made by patient: It includes preconceptional counselling, exact diagnosis and cause of hypertension, patient education, various investigations, close surveillance on hypertension, etc.
The famous quote by Pritchard (1978): “In some mysterious way the presence of chorionic villi in certain women incites vasospasm and hypertension. Moreover, to effect a cure the chorionic villi must be expelled or surgically removed.”26 In one of the interesting studies published recently it has been observed that immediate postpartum curettage is a safe and effective procedure which could accelerate recovery from eclampsia and reduces the severity of complications.27 It is necessary to assess risk-benefit ratio for this procedure considering surgical and anaesthetic complications immediate postpartum in case of eclampsia. But could be promising for unregistered cases from rural area.
 
MATERNAL SEQUELAE OF SEVERE HYPERTENSION IN PREGNANCY28
As we know it is one of the important health hazards in woman's reproductive span. This is mainly because of mortality and morbidity associated with it which could be:
  1. Cerebral vascular accident.
  2. Haemolysis, elevated liver enzymes and low platelets (HELLP).
  3. Convulsions.
  4. Occipital lobe blindness.
  5. Pulmonary oedema.
  6. Aspiration syndrome.
  7. Abruptio placentae.
  8. Postpartem haemorrhage.
  9. Renal failure.
  10. Liver failure and liver rupture.
  11. Deep venous thrombosis.
  12. Complications of treatment like overdose of sedation, aspiration, fluid overload.
  13. Complications of caesarean section.
  14. Fetal complications like IUGR, fetal distress and fetal death.
  15. Sometimes women may get rare complications like massive ascites, which needs intervention like termination, as it cannot be cured by medical treatment. Incidence of it is 21.6/1000 in severe PIH29 and 8probable mechanism includes renal retention of sodium and fluid resulting in expansion of interstitial compartment.30
 
FOLLOW-UP
It is necessary to follow these cases regularly. We normally expect that blood pressure return to normal in 6 weeks. If not so, it is necessary to investigate her for any other underlying causes.
It is always better to explain her and also to all relatives about all happenings specially in cases of eclampsia. In country like India, especially in rural areas, many times husband appears in picture quite late as woman comes for delivery to her mother's place. He need to explained about pre-eclampsia as it can happen in next pregnancies. It has been seen in 20 to 50 per cent cases there is recurrence.31
 
FUTURE
There is definite need for more prospective randomized controlled multicenter trials with sufficient sample size to assess the efficacy of commonly indicated drugs or even changes in dosage of various drugs considering seriousness of this life threatening disease. It is also necessary to have a long-term follow-up of children who underwent trial during their intrauterine life.
 
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