The Pregnant Woman with Chronic Disease

HYPERTENSION IN PREGNANCY PREGNANCY IN A HYPERTENSIVE Amelita C Brillantes, MD, FPCP, FPCC

Objectives:  1. To discuss how pregnancy can alter the pathophysiology of chronic diseases (Hypertension)  2. To discuss any adjustments that should be made in the management of these chronic conditions during pregnancy  3. To discuss precautions that need to be taken in managing these conditions during pregnancy to ensure the safety of both the mother and fetus

What happens to a woman’s body during pregnancy?

Physiological Changes During Pregnancy and Puerperium  Cardiac output increases 30-50% secondary

to increase in blood volume and heart rate.  Blood pressure decreases by 10-15 mm Hg due to a decrease in systemic vascular resistance caused by the creation of a low resistance circuit by the placenta and vasodilatation.  Heart rate increases by 10-15 beats per minute.

 The hematocrit level decreases due to a

disproportionate increase in plasma volume  3rd trimester: supine hypotension of pregnancy

due to decrease in cardiac output due to caval compression by the gravid uterus.  Stroke volume normally increases in the first and second trimester and decreases in the third trimester. This decrease is due to partial vena cava obstruction.

During delivery  Increase in cardiac output, heart rate, blood

pressure, and systemic vascular resistance increase with each uterine contraction.  Delivery-related pain and anxiety aggravate the increase in heart rate and blood pressure.

Post partum  The delivery of the placenta increases

afterload by removing the low resistance circulation and increases the preload by returning placental blood to the maternal circulation.  Blood loss : 300-400 mL during vaginal delivery and 500-800 mL during cesarean delivery.  Postpartum, the cardiac output is typically reduced for 2-6 weeks

Hypertension - the most common medical problem encountered during pregnancy, complicating 2-3% of pregnancies. - among the leading cause of maternal death (15.7%)

Categories  Chronic hypertension  Preeclampsia- Eclampsia  Preeclampsia superimposed on chronic

hypertension  Gestational hypertension (transient hypertension of pregnancy or chronic hypertension identified in the latter half of pregnancy)/ "pregnancy-induced hypertension" (PIH)

Stats  1% of pregnancies are complicated by

chronic hypertension  5-6% by gestational hypertension (without proteinuria)  1-2% by preeclampsia.

Risk factors before pregnancy for the development of hypertensive disorders  High maternal age

 Elevated BP  Dyslipidaemia  Obesity  Positive family history of CVD  Antiphospholipid syndrome  Glucose intolerance

1. Chronic hypertension Definition: ■ BP > or = 140 mmHg systolic or 90 mmHg diastolic prior to pregnancy or before 20 weeks gestation ■ Persists >12 weeks postpartum

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Chronic hypertension  Essential (90%) .  Secondary

-renal parenchymal disease: polycystic kidneys, glomerular or interstitial disease -renal vascular disease: renal artery stenosis, fibromuscular dysplasia -endocrine disorders (eg, adrenocorticosteroid or mineralocorticoid excess, pheochromocytoma, hyperthyroidism or hypothyroidism, growth hormone excess, hyperparathyroidism -coarctation of the aorta -oral contraceptive use

Chronic Hypertension  20-25% of women with chronic hypertension

develop preeclampsia during pregnancy.

Chronic hypertension  Hypertension before pregnancy or during

early pregnancy is associated with a twofold increased risk of GDM gestational diabetes mellitus

Chronic hypertension Chronic hypertensives have an increased RR for  superimposed preeclampsia compared with preeclampsia RR 7.7 95% [CI], (5.7 - 10.1)  caesarean section RR 1.3; ( 1.1 - 1.5)  preterm delivery at < 37 weeks' AOG RR 2.7; ( 1.9 - 3.6)  birth wt < 2.5kg RR 2.7; (1.9 - 3.8)  neonatal unit admission RR, 3.2; (2.2 - 4.4)  perinatal death RR 4.2; (2.7 - 6.5) BMJ. Published online April 15, 2014

Work-up for the Pregnant Hypertensive  tests for target organ damage  potential secondary causes of hypertension  risk factors

Workup for the Pregnant Hypertensive  CBC count with platelets  Urinalysis  Electrolytes  BUN, creatinine  Liver enzymes  Urine dip for protein  24-hour urine collection for creatinine

clearance and protein excretion.  ECG

Thrombocytopenia  Platelet count < 150,000/µL:

75% due to dilutional thrombocytopenia 24% preeclampsia, 1% non pregnacy related platelet disorders  PC < 100,000/µL suggest preeclampsia or ITP immune thrombocytopenic purpura.  If with red cell fragments on PBS: consider hemolytic-uremis syndrome (HUS), TTP thrombotic thrombocytopenic purpura, and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet [count]) should also be considered.

Urinalysis  To screen for proteinuria.  Trace levels to +1 proteinuria are acceptable,  Levels of +2 or greater are abnormal and

should be quantified with a 24-hour urine collection or spot urine protein-creatinine ratio.

Urine protein:Crea ratio  Abnormal Spot urine specimens for protein-

   

creatinine ratios can predict the presence of abnormal proteinuria during pregnancy. Ratio > 0.7 mg protein/mg creatinine : 85% sensitive at predicting significant proteinuria Ratio < 0.15 : rule out. Spot ratio more accurate than urinalysis Need confirmation with a 24-hour urine collection

24 Hr collection for urinary protein  Normal range is up to 300 mg/d.  > 300 mg/day: renal involvement in

preeclampsia.

Creatinine/ Creatinine Clearance  Serum creatinine is usually < than 0.8 mg/dL

during pregnancy  Higher levels suggest intravascular volume contraction or renal involvement in preeclampsia  Creatinine clearance increases approximately 50% during pregnancy  CC levels < 100 mL/min suggest renal dysfunction : chronic or due to preeclampsia.

2. Preeclampsia  BP > = 140 mmHg systolic or 90 mmHg

diastolic with proteinuria (>300 mg/24 hrs) after 20 weeks gestation ■ Can progress to eclampsia (seizures) ■ More common in nulliparous women, multiple gestation, women with hypertension for >4 years, family history of preeclampsia, hypertension in previous pregnancy, renal disease JNC7

2. Preeclampsia  a disorder of placental dysfunction leading to a

syndrome of endothelial dysfunction with associated vasospasm, with arterial constriction and relatively reduced intravascular volume compared with that of a normal pregnancy.  an altered maternal immune response to fetal/placental tissue may contribute to the development of preeclampsia.

Preeclampsia  Women who develop preeclampsia have an

increased risk of recurrent preeclampsia during subsequent pregnancies: 18%.  The risk is higher (50%) in women who develop severe early preeclampsia (ie, before 27 weeks' gestation).  These women are also at increased risk for cardiovascular disease later in life.

Maternal personal risk factors for preeclampsia First pregnancy New partner/paternity Age younger than 18 years or older than 35 years History of preeclampsia Family history of preeclampsia in a first-degree relative  Black race  Obesity (BMI ≥30)  Interpregnancy interval less than 2 years or longer than 10 years     

Maternal medical risk factors for preeclampsia  Chronic hypertension, especially when secondary to       

such disorders as hypercortisolism, hyperaldosteronism, pheochromocytoma, or renal artery stenosis Preexisting diabetes, especially with microvascular disease Renal disease SLE Obesity Thrombophilia History of migraine Use of selective serotonin uptake inhibitor antidepressants (SSRIs) beyond the first trimester

Preeclampsia  The pregnant woman may manifest

dysfunction of multiple organ systems:CNS, hepatic, pulmonary, renal, and hematologic systems.  Endothelial damage leads to pathologic capillary leak that can present in the mother as rapid weight gain, nondependent edema (face or hands), pulmonary edema, hemoconcentration, or a combination thereof.

Ophthalmologic findings in preeclampsia  Retinal vasospasm is a severe manifestation

of maternal disease -consider delivery.  Retinal edema (serous retinal detachment)manifest as severely impaired vision if the macula is involved - reflects severe preeclampsia - deliver. This typically resolves upon completion of pregnancy and resolution of the hypertension and fluid retention.

Gastrointestinal findings in preeclampsia  Right upper quadrant (RUQ) abdominal

tenderness from liver swelling and capsular stretch. Consider delivery.

Neurologic Findings  Brisk, or hyperactive, reflexes are common

during pregnancy  Clonus is a sign of neuromuscular irritability that usually reflects severe preeclampsia.  Visual disturbances -scintillations and scotomata, (due to cerebral vasospasm)  New-onset headache-frontal, throbbing, or similar to a migraine headache

Life-threatening complications in preeclampsia  Eclamptic seizures  Intracerebral Hemmorhage  Pulmonary edema (due to capillary leak,

myocardial dysfunction, excess IV fluid administration),  Acute renal failure (due to vasospasm, acute tubular necrosis [ATN], or renal cortical necrosis),

Life-threatening complications in preeclampsia  Proteinuria greater than 4-5 g/d  HELLP syndrome (microangiopathic hemolysis, elevated liver enzymes, and thrombocytopenia [platelets < 100/µL])  Hepatic swelling with or without liver dysfunction, hepatic infarction/rupture and subcapsular hematoma (which mayleadtomassiveinternal hemorrhage and shock),  DIC and/or consumptice coagulopathy (rare).

Preeclampsia Treatment  Hospitalization for bed rest  Control of BP  Seizure prophylaxis in the presence of signs

of impending eclampsia  Timely delivery.

Timely delivery  < 32 weeks not good for fetus  At any time, if with fetal distress or

intrauterine growth retardation  Maternal considerations: severe hypertension, hemolysis, elevated liver enzymes, low platelet count, deteriorating renal function, visual disturbance, and headache or epigastric pain.  Vaginal delivery is preferable to cesarean delivery to avoid the added stress of surgery. JNC7

3. Chronic Hpn with superimposed preeclampsia  New onset proteinuria after 20 weeks in a 

  

woman with hypertension Sudden two- to threefold increase in proteinuria in a woman with hypertension and proteinuria prior to 20 weeks gestation Sudden increase in BP Thrombocytopenia Elevated AST or ALT JNC7

4.Gestational hypertension  Hypertension without proteinuria occurring  

 

after 20 weeks gestation Temporary diagnosis May represent preproteinuric phase of preeclampsia or recurrence of chronic hypertension abated in midpregnancy May evolve to preeclampsia If severe, may result in higher rates of premature delivery and growth retardation than mild preeclampsia JNC7

Gestational hypertension  1/3 will develop the syndrome of

preeclampsia  in the absence of preeclampsia, maternal and fetal outcomes are usually normal.  Gestational hypertension may be a harbinger of chronic hypertension later in life.

Hypertension Treatment

Treat? 1. These women are at low risk for cardiovascular complications within the short time frame of pregnancy with good maternal and neonatal outcomes. 2. Although it might be beneficial for the hypertensive mother, a reduction in blood pressure may impair uteroplacental perfusion and thereby jeopardize fetal development. 3. Data on pharmacological treatment of mild to moderate hypertensive pregnant women largely originate from trials that were too small to be able to detect a predictably modest reduction in obstetrical complications.

 Some clinicians prefer to stop

antihypertensive medications while maintaining close observation including use of home BP monitoring.  Meta-analysis of 45 RCTs of treatment with several classes of antihpn drugs in st 1 and 2 hypertension during pregnancy: Decreased BP: SGA infants independent of type of hypertension, type of antihypertensive agent, and duration of therapy JNC7

 For pregnant women with TOD, BP meds should

be continued as needed  Treatment should be re-instituted once BP reaches 150–160 mmHg or 100–110 mmHg diastolic, in order to prevent increases in BP to very high levels during pregnancy.  Aggressive treatment of severe chronic hypertension in the first trimester is critical, since fetal loss rates of 50 percent and significant maternal mortality have been reported in these women  Fetal loss and acceleration of maternal renal disease increase at serum creatinine levels >1.4 JNC7 mg/dL at conception.

ESC Guidelines  While there is consensus that drug treatment of

severe hypertension in pregnancy (>160 forSBP or >110 mmHgfor DBP) is required and beneficial, the benefits of antihypertensive therapy are uncertain for mildly to moderately elevated BP in pregnancy (140/90mmHg in women with  (i) gestational hypertension (with or without proteinuria),  (ii)preexisting hypertension with the superimposition of gestational hypertension or  (iii) hypertension with asymptomatic OD or symptoms at any time during pregnancy. ESC 2013

ESC 2013

 A systolic blood pressure >= 170 or a diastolic

blood pressure>= 110 mmHg should be considered an emergency requiring hospitalization.  Under emergency circumstances, a reduction in blood pressure may be obtained by intravenous labetalol, oral methyldopa, or oral nifedipine

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ACOG 2011 Committee Opinions  Intravenous labetalol and hydralazine are

both considered first-line medications for the management of acute-onset, severe hypertension in pregnant and postpartum women  Parenteral hydralazine may increase the risk of maternal hypotension (systolic BP 90 mm Hg or less)  Parenteral labetalol may cause neonatalbradycardia and should be avoided in women with asthma or heart failure

 No significant changes in umbilical blood flow

have been observed with the use of either labetalol or hydralazine and maternal and perinatal outcomes are similar for both drugs

 In pre-eclampsia associated with pulmonary

oedema, nitroglycerin is the drug of choice.  In non-severe hypertension and out-ofemergency situations, methyldopa, labetalol, and calcium antagonists are the preferred drugs.

 Atenolol should be given with caution during

pregnancy because of reports of an association with fetal growth retardation which is related to the duration of treatment.  ACE inhibitors and angiotensin receptor antagonists should never be used in pregnancy.  Unless there is oliguria, diuretic therapy is inappropriate in pre-eclampsia, in which plasma volume is reduced

Low dose ASA to prevent Preeclampsia  Controversial  75mg aspirin daily from 12 weeks until delivery, provided with low risk of GI bleeding

ESC 2013

ASA for Women at high risk of preeclampsia  hypertension in a previous pregnancy  CKD  Autoimmune disease such as systemic

lupus erythematosus, or antiphospholipid syndrome  type 1 or 2 diabetes  chronic hypertension ESC 2013

ASA for Women with more than one moderate risk factor for preeclampsia      

first pregnancy age >40 years Pregnancy interval of >10 years BMI >35 kg/m2 at first visit Family history of preeclampsia multiple pregnancy Esc 2013

 Magnesium sulfate i.v. has been proved

effective in the prevention of eclampsia and the treatment of seizures.  Induction of delivery is appropriate in gestational hypertension with proteinuria and adverse conditions such as visual disturbances, coagulation abnormalities or fetal distress.

Treating hypertension during lactation.  Hypertensive mothers can usually breast-

feed safely.  All antihypertensive drugs that have been studied are excreted into human breast milk.  In mothers with stage 1 hypertension who wish to breast-feed for a few months, it might be prudent to withhold BP meds, with close monitoring of BP, and reinstitute therapy following discontinuation of nursing.

During lactation  No short-term adverse effects have been

reported from exposure to methyldopa or hydralazine.  Propanolol and labetalol are preferred if a BB is indicated.  ACEIs and ARBs should be avoided, based on reports of adverse fetal and neonatal renal effects.  Diuretics may reduce milk volume and thereby suppress lactation.

Prognosis and Follow up  Women with previous gestational

hypertension seem to be at increased risk for cardiovascular disease in later life.

Long-term cardiovascular consequences in gestational hypertension  Women with a historyof preeclampsia have approximately double the risk of subsequent ischaemic heart disease, stroke and venous thrombo-embolic events over the 5–15 years after pregnancy  The risk of developing hypertension is almost fourfold  Women with early-onset preeclampsia (delivery before 32 weeks of gestation), with stillbirth or foetal growth retardation are considered at highest risk.

Long term Ffup  Women with preeclampsia require follow-up

after hospital discharge to ensure normalization of blood pressure and any noted laboratory abnormalities  Blood pressure changes due to preeclampsia usually resolve within days to weeks after delivery but may persist for 3 months.  Persistent hypertension beyond this point probably represents chronic hypertension.

Long term Ffup  Laboratory abnormalities related to

preeclampsia (eg, proteinuria, thrombocytopenia, liver enzyme elevations) should be followed until the abnormalities return to the reference range.  Failure to normalize warrants an evaluation for other acute or chronic medical disorders with potential long-term consequences.

 End.  May all your dreams come true.  Enjoy the HOT summer!

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