1. Pregnancy Induced Hypertension
Hypertensive disorders are among the most common and yet serious conditions seen in obstetrics. These disorders cause substantial morbidity and mortality for both mother and fetus, despite improved prenatal care.
Jun Ma
Dept. of Obstetrics & Gynecology
The First Hospital of Xi’an Jiaotong Univ

2. Introduction Incidence: China: 9.4%, worldwide: 7-12%
The most common and yet serious conditions seen in obstetrics
cause substantial morbidity and mortality in the mother and fetus
Death due to cerebral hemorrhage, aspiration pneumonia, hypoxic encephalophathy, thromboembolism, hepatic rupture, renal failure
Hypertensive disorders are among the most common and yet serious conditions seen in obstetrics. These disorders cause substantial morbidity and mortality in both the mother and fetus, despite improved prenatal care.

3. Hypertension in pregnancy
Definition
Diastolic BP ≥90 mmHg
Systolic BP ≥140 mmHg
Or as an increase in the diastolic BP of ≥ 15 mmHg or in the systolic blood pressure of 30 mmHg, as compared to previous pressure
The increased blood pressures be present on at least two separate occasions, > 6h apart
Although this definition seems quite clear, its use in clinical practice is difficult because of various problems in obtaining a reliable assessment of blood pressure.
Position
Corrrect size blood pressure cuff
BP normally decreases during the second trimester, and the decrease may mask the presence of chronic hypertension .

4. Classification
Various classifications of hypertensive disorders in pregnancy have been proposed. Here the commonly used classification of ACOG is proposed.

5. Classification of Hypertensive Disorders in Pregnancy (ACOG)
Pregnancy-induced hypertension
Preeclampsia
Mild
Severe
Eclampsia
Chronic hypertension preceding pregnancy
Chronic hypertension with superimposed PIH
Superimposed preeclampsia
Superimposed eclampsia
Gestational hypertension
Hypertensive disorders in pregnancy represent a spectrum of disease, classification systems should not be considered as rigid markers on which all management decisions are made.

6. Classification (1) Pregnancy-induced hypertension:
Hypertension associated with proteinuria and edema, occurring primarily in nulliparas after the 20th week or near term.
Preeclampsia
【mild 】
BP ≥ 140/90mmHg
Onset after 20 weeks’ gestation
Proteinuria (>300mg/24-hr urine collection) or +
Epigastric discomfort
Thrombocytopenia

7. Classification (2) 【severe】 BP ≥ 160/110 mmHg
Marked proteinuria (>1-2 g/24-hr urine collection or 2+ or more), oliguria
Cerabral or visual disturbances such as headache and scotomata
Pulmonary edema or cyanosis
Epigastric or right upper quadrant pain (probably caused by subcapsular hepatic hemorrhage)
Evidence of hepatic dysfunction, or thrombocytopenia

8. Classification (3) Eclampsia Meets the criteria of preeclampsia
Presence of convulsions, not attributable to other neurological disease,
Occurrence: %, with 25% occurring in the 1st 72 hs postpartum

9. Classification (4)
Chronic hypertension proceeding pregnancy (essential or secondary to renal disease, endocrine disease, or other causes)
BP ≥ 140/90 mmHg
Presents before 20 wk gestation
Persists beyond 12 wk postpartum

10. Classification (5)
Chronic hypertension with superimposed preeclampsia or eclamptia
Coexistence of preeclampsia or eclampsia with preexisting chronic hypertension
Cause greatest risk
When diagnosis is obscure, it is always wise to assume that the findings represent preeclampsia and treat accordingly.
Superimposed preeclampisa: preeclampsia may occur in women with chronic hypertension, the progress is worse for the mother and the fetus than either condition alone. The criteria for it are worsening hypertension before 20 weeks together with either nondependent edema or proteinuria.

11. Classification (6) Gestational hypertension: not mentioned in the ACOG
Finding of hypertension in late pregnancy in the absence of other findings suggestive or preeclampsia
Transient hypertension of pregnancy
May develop into chronic hypertension if elevated BP persists beyond 12 weeks postpartum
Gestational hypertension: is further divided into transient hypertension of pregnancy if preeclampsia is present at the time of delivery and the blood pressure is normal by 12 weeks postpartum, and chronic hypertension if the elevation in blood pressure persists beyond 12 weeks postpartum. This condition is often predictive of the later development of essential hypertension.

12. High risk factors Nulliparous
<18ys or >40 ys, multiple pregnancy
Has previous gestational hypertensive disorders
Chronic nephritis
Diabetic
Malnutrition
Low social status
Hydatidiform mole

13. Etiology: UNCLEAR
Immune mechanism (rejection phenomenon, insufficient blocking Ab)
Injury of vascular endothelium----disruption of the equilibrium between vasoconstriction and vasodilatation, imbalance between PGI and TXA
Compromised placenta profusion
Genetic factor
Dietary factors: nutrition deficiency
Insulin resistance
Increase CNS irritability
Preeclampsia has been described as a disease of theories, because the cause is unknown.

14. Pathophysiology
Hypertension in pregnancy affects the mother and newborn to varying degrees, depending on the severity of disease. The effect is multisystem. One common pathophysiologic finding in hypertension in pregnancy , especially when there is progression to preeclampsia, is vasospasm.

15. Central nervous system
Raised BP disrupt autoregulation
Increased permeability due to vasospasm---thrombosis of arterioles, microinfarcts, and petechial hemorrhage
Cerebral edema: increased intracranial pressure
CT scan (1/3-1/2 positive): focal hypodensity
Cerebral angiography: diffuse arterial vasoconstriction
EEG: nonspecific abnormality (75% in eclamptic patient)

16. Eyes
Serous retinal detachment
Cortical blindness

17. Pulmonary system Pulmonary edema Cardiogenic or noncardiogenic
Excessive fluid retention, decreased hepatic synthesis of albumin, decreased plasma colloid oncotic pressure,
Often occurs postpartum
Aspiration of gastric contents: the most dreaded complications of eclamptic seizures

18. Kidneys Characteristic lesion of preeclampsia: glomeruloendotheliosis
Swelling of the glomerular capillary endothelium
Decreased GFR
Fibrin split products deposit on basement membrane
Proteinuria
Increase of plasma uric acid, creatinine,

19. Liver The spectrum of liver disease in preeclampsia is broad
Subclinical involvement
Rupture of the liver or hepatic infarction
HELLP syndrome: hemolysis, elevated liver enzymes and low platelets

20. Cardiovascular system
Generalized vasoconstriction, low-output, high-resistance state
Untreated preeclamptic women are significantly volume-depleted
Capillary leak
Cardiac ischemia, hemorrhage, infarction, heart failure
Increased sensitivity to vasoconstrictor effects of angiotensin

21. Blood (1) Volume: reduced plasma volume
Normal physiologic volume expansion does not occur
Generalized vasoconstriction and capillary leak
Hematocrit

22. Blood (2): coagulation Isolated thrombocytopenia: <150,000/ml
Microangiopathic hemolytic anemia
DIC (5%)
HELLP syndrome: in severe preeclampsia
schistocytes on the peripheral blood smear
lactic dehydrogenase > 600 u/L
total bilirubin > 1.2 mg/dl
aspartate aminotransferase >70 U/L
platelet count <100,000/mm3
Misdiagnosis: hepatitis, gallbladder disease, ITP
ITP: idiopathic thrombocytopenic purpura

23. Endocrine system
Vascular sensitivity to catecholamines and other endogenous vasopressors such as antidiuretic hormone and angiotensin II is increased in preeclampsia
Disequilibrium of prostacyclin/ thromboxane A2

24. Placenta perfusion 500 mm vs 200 mm
Acute atherosis of spiral arteries: fibrinoid necrosis of the arterial wall, the presence of lipid and lipophages and a mononuclear cell infiltrate around the damaged vessel----vessel obliteration---- placental infarction
Fetus is subjected to poor intervillous blood flow
IUGR or stillbirth

25. Clinical findings (1) Symptoms and signs Hypertension
Diastolic pressure ≥ 90 mmHg or
Systolic pressure ≥ 140 mmHg or
Increase of 30/15 mmHg
Proteinuria
>300 mg/24-hr urine collection or
+ or more on dipstick of a random urine
Hypertension is the most important criterion for the diagnosis of preeclampsia, and it may occur suddenly. The criteria are as described before. It usually falls during sleep in patients with mild preeclampsia and chronic hypertension, but in severe preeclampsia, BP may increase during sleep, eg, the most severe hypertension may occur at 2 am.
Proteinuria is the last sign to develop. Eclampsia may occur without proteinuria. Most patients with proteinuria will have glomeruloendotheliosis on kidney biopsy. Proteinuria in preeclampsia is an indicator of fetal jeopardy. The incidence of SGA infants and perinatal mortality is mardedly increased in patients with proteinuric preeclampsia.

26. Clinical findings (2) Edema
Weight gain: 1-2 lb/wk or 5 lb/wk is considered worrisome
Degree of edema
Preeclampsia may occur in women with no edema
Most recent reports omit it from the definition

27. Clinical findings (3)
Differing clinical picture in preeclampsia-eclampsia crises: patient may present with
Eclamptic seizures
Liver dysfunction and IUGR
Pulmonary edema
Abruptio placenta
Renal failure
Ascites and anasarca
Preeclampsia-eclampsia is a multisystem dissease with varying clinical presentations.

28. Laboratory findings (1)
Clinical findings (4)
Laboratory findings (1)
Blood test: elevated Hb or Hct, in severe cases, anemia secondary to hemolysis, thrombocytopenia, FDP increase, decreased coagulation factors
Urine analysis: proteinuria and hyaline cast, specific gravity > 1.020
Liver function: ALT and AST increase, alkaline phosphatase increase, LDH increase, serum albumin
Renal function: uric acid: 6 mg/dl, serum creatinine may be elevated

29. Laboratory findings (2)
Clinical findings (5)
Laboratory findings (2)
Retinal check:
Other tests: ECG, placenta function, fetal maturity, cerebral angiography, etc

30. Differential diagnosis
Pregnancy complicated with chronic nephritis
Eclampsia should be distinguished from epilepsy, encephalitis, brain tumor, anomalies and rupture of cerebral vessel, hypoglycemia shock, diabetic hyperosmatic coma

31. Complications Preterm delivery
Fetal risks: acute and chronic uteroplacental insufficiency
Intrapartum fetal distress or stillbirth
IUGR
Oligohydramnios

32. Predictive evaluation (1)
Mean arterial pressure, MAP= (sys. Bp + 2 x Dia. Bp) /3
MAP> 85 mmHg: suggestive of eclampsia
MAP > 140 mmHg: high likelihood of seizure and maternal mortality and morbidity
More than 100 clinical , biophysical and biochemical tests have been reported to predict preeclampsia, unfortunately, most suffer from poor sensitivity and none are suitable for routine use a as screening test in clinical practice.

33. Predictive evaluation (2)
Roll over test: ROT
Preeclamptic patients are more sensitive to angiotensin II
Difference between Bp obtained at left recumbent position and supine position (at a 5 min interval)
Positive: > 20 mmHg
Urine calcium/ creatinine < 0.04
Several authors have reported reduced urinary excretion of calcium during preeclampsia and for several weeks prior to the onset of clinically apparent disease. In addition, abnormal intracellular calcium metabolism in platelets and RBC has been demonstrated in women with preeclampsia as compared with normotensive pregnant women.

34. Prevention
Calcium supplementation: not effective in low risk women bur show effect in high risk group
Aspirin (antithrombotic): uncertain
Good prenatal care and regular visits
Baseline test for high-risk women
Eclampsia cannot always be prevented, it may occur suddenly and without warning.
As a result, most studies of prevention have used patients with various risk factors for preeclampsia.
Aspirin: There is evidence to suggest that thromboxane A2 production is markedly increased, while prostacyclin production is reduced in women with welll established preeclampsia and prior to the onset of preeclampsia. In addition, placental infarcts and thrombosis of the spiral arteries have been demonstrated in pregnancies complicated by preeclampsia, particularly in those with severe fetal growth retardation or fetal demise. As a result of these findings, several authors have used various antithrombotic agents in a an attempt to prevent preeclampsia.
The baseline tests include:
Hct and Hb, platelet count
Serum creatine and uric acid
24-h urine collection for protein and creatinine clearance
Early ultrasounds and follow-up scans.

35. Treatment Mild preeclampsia: bed rest & delivery
Hospitalization or home regimen
Bed rest (position and why) and daily weighing
Daily urine dipstick measurements of proteinuria
Blood pressure monitoring
Fetal heart rate testing
Periodic 24-h urine collection
Ultrasound
Liver function, renal function, coagulation
The patient is usually hospitalized upon diagnosis, since this diminishes the possibility of convulsions and enhances the chance of fetal survival. Hospitalization to prevent premature delivery in preeclmapsia is far less expensive than the cost of caring for a premature infant.
The mainstay of patients with mild preeclampsia and an immature fetus is bed rest, preferably with as much of the time as possible spent in a lateral decutitus position. In this position cardia function and uterine blood flow are maximized and maternal BP in most cases are normalized. This improves uteroplacental function, allowing normal fetal growth and metabolism.

36. A. Mild preeclampsia: bed rest & delivery
Observe for danger signals: severe headache, epigastric pain, visual disturbances
Sedatives: debatable

37. B. Severe preeclampsia:
Prevention of convulsion: magnesium sulfate or diazepam and phenytoin
Control of maternal blood pressure: antihypertensive therapy
Initiation of delivery: the definitive mode of therapy if severe preeclampsia develops at or > 36 wk or if there is evidence of fetal lung maturity or fetal jeopardy.

38. Magnesium sulfate
Decreases the amount of acetylcholine released at the neuromuscular junction
Blocks calcium entry into neurons
Vasodilates the smaller-diameter intracranial vessels

39. Magnesium sulfate Prevent convulsion
Virtually ineffective on blood pressure
i.v. or i.m.
5g loading dose 5-10 min, i.v.
1-2g/hr constant infusion
Total dose: g/d

40. Toxicity:
Diminished or loss of patellar reflex
Diminished respiration
Muscle paralysis
Blurred speech
Cardiac arrest

41. How to prevent toxicity?
Frequent evaluation of patellar reflex and respirations
Maintenance of urine output at >25 ml/hr or 600 ml/d
Reversal of toxicity:
Slow i.v . 10% calcium gloconate
Oxygen supplementation
Cardiorespiratory support

42. Antihypertensive therapy: reduce the Dia. pressure to 90-110 mmHg
Indication
Bp> 160/110 mmHg
Dia. Bp > 110 mmHg
MAP > 140 mmHg
Chronic hypertension with previous antihypertensive drugs usage

43. Antihypertensive therapy
Medications:
Hydrolazine: initial choice
Labetolol
Nifedipine
Nimoldipine
Methyldoe
Sodium nitroprusside

44. Mechanism Effects Medication of action Direct peripheral vasodilation
CO, RBF maternal flushing,
headache, tachycardia
hydralazine
CO, RBF maternal flushing,
headache, neonatal depressed respirations
a, b- adrenergic
blocker
labetalol
CO, RBF maternal orthostatic hypotension
Headache, no neonatal effects
Calcium channel
blocker
nifedipine
Direct peripheral
arteriolar vasodilation
CO, RBF maternal flushing,
headache, tachycardia
methyldopa
sodium nitroprusside
Direct peripheral
vasodilation
Metabolite (cyanide)
toxic to fetus

45. Plasma expander
Diuretics

46. Delivery Indication of termination of pregnancy
Preeclampsia close to term
<34 wk with decreased placental function
2 hs after control of seizure

47. Delivery Induction of labor
First stage: close monitor, rest and sedation
Second stage: shorten as much as possible
Third stage: postpartum hemorrhage
Cesarean section
Induction of labor unsuccessful
Induction of labor not possible
Maternal or fetal status is worsening
Postpartum eclampsia can happen at days after delivery.

48. Eclampsia No aura preceding seizure Multiple tonic-clonic seizures
Unconsciousness
Hyperventilation after seizure
Tongue biting, broken bones, head trauma and aspiration, pulmonary edema and retinal detachment

49. Management Control of seizure Control of hypertension Delivery
Proper nursing care