Hypertensive disorders of pregnancy - Australian Prescriber

VOLUME 35 : NUMBER 2 : APRIL 2012articleHypertensive disorders of pregnancyphysiological fall in blood pressure that occurs duringthe first trimester leads to normalisation without theneed for medication. There is no direct evidence thatcontinued treatment of chronic hypertension leads toa reduction in the risk of adverse pregnancy events. 3Benefits appear to be confined to reducing severehypertension (≥170/110 mmHg), however most centresstart or continue antihypertensive drugs when bloodpressure exceeds 160 mmHg systolic and/or100 mmHg diastolic on more than one occasion. 3Table 2 outlines the antihypertensive drugs mostcommonly used in pregnancy. 3,4Blood pressure reduction to 140–160 mmHg systolicand 90–100 mmHg diastolic are acceptable treatmentgoals. Stricter blood pressure control may be associatedwith fetal growth restriction, presumed to be relatedto relative placental hypoperfusion. Importantly,women need to be carefully monitored for any signsof pre-eclampsia which may include worseninghypertension and new or worsening proteinuria (seeBox). Repeated assessment of fetal wellbeing andgrowth is appropriate, although given that there areno guidelines, the frequency of monitoring is usuallyat the discretion of the woman’s treating obstetrician.Gestational hypertensionGestational hypertension is defined as:••new onset of hypertension after 20 weeksgestation••no other features to suggest pre-eclampsia(see Box)••normalisation of blood pressure within threemonths postpartum.Gestational hypertension is associated with adversepregnancy outcomes. These are more common if itpresents earlier in the pregnancy, if it progresses topre-eclampsia or if hypertension is severe(≥170/110 mmHg). 3Although rare, phaeochromocytoma can initiallypresent in pregnancy. It can be fatal. Investigationis needed if there are any other features to suggesta phaeochromocytoma (for example paroxysmalhypertension, episodic headache and sweating),or if the onset of hypertension occurs early inthe pregnancy or is severe. Plasma or urinarymetanephrines (catecholamine metabolites) tendnot be affected by the physiological changes ofpregnancy and are useful as screening investigations. 5The benefits of treating mild to moderate hypertensionare limited to the prevention of severe hypertension andappear to have no effect on the potential for adversepregnancy outcomes. The indications for treatmentwith antihypertensive drugs, goals of therapy and thechoice of drug are similar to the treatment of chronichypertension in pregnancy (Table 2). Up to 25% ofwomen who develop hypertension in pregnancy willeventually be diagnosed with pre-eclampsia, even ifno other manifestations are present initially. Regularmonitoring of blood pressure, and investigation forproteinuria and other features of pre-eclampsia (up toonce or twice per week) is reasonable. 3By definition, gestational hypertension should resolvewithin three months postpartum and the patient cangenerally be weaned off antihypertensive drugs withinweeks. If hypertension has not resolved within threemonths, an alternative diagnosis – for example chronic(essential or potentially secondary) hypertension –needs to be considered. There is a risk of recurrencein subsequent pregnancies so increased monitoringwill be required.Pre-eclampsia, eclampsia andsuperimposed pre-eclampsiaThe aetiology of pre-eclampsia is unclear althougha combination of maternal and placental factors arelikely to contribute. Abnormal placental formation,resulting in aberrant angiogenic factor production andsystemic endothelial dysfunction, as well as geneticand immunological factors, are thought to play a role.Risk factors include nulliparity, age less than 18 or morethan 40 years, a past history of pre-eclampsia andmaternal medical comorbidities (hypertension, diabetesmellitus, renal disease, obesity, antiphospholipidantibodies or other thrombophilia and connective tissuedisease). 6 Pre-eclampsia is associated with fetal growthrestriction, preterm delivery, placental abruption andBox Features of pre-eclampsiaHypertension with onset after 20 weeks gestationRenal manifestationsSignificant proteinuriaSerum creatinine >90 micromol/L (or renal failure)OliguriaHaematological manifestationsDisseminated intravascular coagulationThrombocytopeniaHaemolysisHepatic manifestationsRaised serum transaminasesSevere right upper quadrant or epigastric painNeurological manifestationsEclamptic seizureHyperreflexia with sustained clonusSevere headachePersistent visual disturbancesStrokePulmonary oedemaFetal growth restrictionPlacental abruption48Full text free online at www.australianprescriber.com

VOLUME 35 : NUMBER 2 : APRIL 2012articleperinatal death. 7 Severe pre-eclampsia has the potentialfor progression to eclampsia, multi-organ failure, severehaemorrhage and rarely maternal mortality.Pre-eclampsia is a disorder with many manifestations.New onset hypertension after 20 weeks gestationand proteinuria are the most common presentingfeatures. A urine dipstick for proteinuria can be auseful screening test, but is confounded by highfalse positive and false negative rates. If there is anyuncertainty, assessment of the urine protein:creatinineratio is advised. Peripheral oedema is no longerconsidered a diagnostic feature of pre-eclampsia asit is neither a sensitive nor specific sign. Other clinicalmanifestations are outlined in the Box, with theirpresence suggesting severe pre-eclampsia.The presence of severe pre-eclampsia mandatesurgent review. A multidisciplinary team approach(obstetrician, midwife, neonatologist, anaesthetistand physician) is often required. Delivery is the onlydefinitive management for pre-eclampsia. The timingof delivery is dependent on the gestational age andwell-being of the fetus and the severity of thepre-eclampsia. The pregnancy is rarely allowed togo to term. Management of pre-eclampsia before32 weeks gestation should occur in specialist centreswith sufficient expertise and experience. Severehypertension may require parenteral antihypertensivedrugs (such as hydralazine), which should only be givenin a suitably monitored environment (birth suite or highdependency unit). Intravenous magnesium sulfate isgiven for the prevention of eclampsia in severe cases. 8Although pre-eclampsia progressively worsens whilethe pregnancy continues, outpatient managementmay be considered in selected cases. Theantihypertensive drugs used in pre-eclampsia arethe same as those used to treat chronic andgestational hypertension (Table 2). 3 The treatmentgoals for blood pressure control are also the same(140–160 mmHg systolic and 90–100 mmHgdiastolic). Although widely advised in the past,there is little evidence to support bed rest. Giventhe potential for venous thromboembolism fromimmobilisation, bed rest is generally only advisedwith severe, uncontrolled hypertension. 9Postpartum management and secondarypreventionMost of the manifestations of pre-eclampsia resolvewithin the first few days or weeks postpartum. Thefeatures of pre-eclampsia, including hypertension,may worsen before they improve. Rarely the firstmanifestations occur postpartum. Frequent reviewof blood pressure during this period is essential, forexample once to twice weekly. Antihypertensivedoses are reduced or ceased when the bloodpressure falls to less than 140/90 mmHg. Home bloodpressure monitoring with an automated device canbe helpful to avoid hypotension. This is a commonoccurrence, as the features of pre-eclampsia andtherefore antihypertensive requirements can recedeprecipitously. Like gestational hypertension, if theblood pressure does not normalise within threemonths consider an alternative diagnosis. It is alsoimportant to confirm that proteinuria has resolved.Pre-eclampsia can recur in subsequent pregnancieswith the most prominent risk factors being previoussevere or early onset pre-eclampsia or chronichypertension. The use of low-dose aspirin has beenshown to be safe and beneficial in decreasing thisrisk in women with a moderate to high risk ofpre-eclampsia. Aspirin is therefore generally advisedin subsequent pregnancies. It is started at the end ofthe first trimester and can be safely continued untilthe third trimester, with most centres ceasing therapyat 37 weeks gestation. Calcium supplements(1.5 g/day) may be of benefit, particularly in women atrisk for low dietary calcium intake. The administrationof vitamin C and E supplements has not been shownto be beneficial and may be harmful. 3Table 2 Relatively safe antihypertensive drugs in pregnancyAntihypertensive Class Starting dose Maximum dose Important adverse effectsLabetalol Beta blocker 100–200 mg twice a day 400 mg three times a day Bradycardia, bronchospasm, transient scalptinglingOxprenolol Beta blocker 40–80 mg twice daily 80–160 mg twice daily Bradycardia, bronchospasmNifedipineCalcium channelantagonist10 mg twice a day, 30 mgdaily controlled release20–40 mg twice a day,120 mg daily controlledreleaseSevere headache, peripheral oedemaMethyldopa Centrally-acting 250 mg twice a day 500 mg four times a day Sedation, light-headedness, dry mouth, nasalcongestion, haemolytic anaemia, depressionHydralazine Vasodilator 25 mg twice a day 50–200 mg total daily dose Flushing, headache, lupus-like syndromePrazosin Alpha blocker 0.5 mg twice a day 3 mg total daily dose Postural hypotensionFull text free online at www.australianprescriber.com49

VOLUME 35 : NUMBER 2 : APRIL 2012articleHypertensive disorders of pregnancySelf-testquestionsTrue or false?3. Aspirin can be used toprevent the recurrenceof pre-eclampsia infuture pregnancies.4. Gestationalhypertension increasesthe risk of futurecardiovascular disease.Answers on page 71Antihypertensive drugs postpartumThe choice of antihypertensive drugs depends onwhether breastfeeding is attempted. When thewoman wishes to breastfeed, consideration must begiven to potential transfer of the drug into breast milk.Most drugs safely used in pregnancy are excreted inlow amounts into breast milk and are compatible withbreastfeeding. Table 3 shows antihypertensive drugsto use or avoid during lactation. 4 Should there be nodesire to breastfeed and adequate contraception isused, the choice of antihypertensive drug is the sameas for any other non-pregnant patient.Long-term follow-upPre-eclampsia and gestational hypertensionappear to be associated with an increased longtermrisk of cardiovascular disease, includinghypertension, ischaemic heart disease, stroke andvenous thromboembolism. 10 There may also bea small increased risk of chronic renal failure andthyroid dysfunction after pre-eclampsia. 11,12 Annualassessments of blood pressure and at least five-yearlyassessments for other cardiovascular risk factors areadvisable. 3 Thyroid and renal function should also bemeasured intermittently.ConclusionPregnancies affected by hypertensive disordersrequire careful monitoring due to the increasedrisks of adverse pregnancy outcomes. New onsethypertension in pregnancy warrants consideration ofpre-eclampsia. Antihypertensive drugs for all formsof hypertensive disorder of pregnancy tend to bereserved for persistent or severe hypertension. Manystandard antihypertensive drugs are contraindicatedin pregnancy and lactation. In women at moderateto high risk for recurrent pre-eclampsia, prophylaxiswith low-dose aspirin and calcium supplementsin subsequent pregnancies may be of benefit.Long-term follow-up, particularly in regard tocardiovascular risk, is important in women with ahistory of hypertensive disorders in pregnancy.Conflict of interest: none declaredTable 3 Antihypertensive drugs during breastfeedingClass Drugs considered safe Avoid – potentially harmful, no or limited dataBeta blockers Propranolol, metoprolol, labetalol Avoid atenolol, no data for other beta blockersCalcium channel antagonists Nifedipine More limited data for diltiazem and verapamil – may be safe;avoid other calcium channel blockersACE inhibitors Captopril, enalapril Other ACE inhibitorsAngiotensin receptor blockers None No dataThiazide diuretics None Limited dataOther Methyldopa, hydralazine Limited data for prazosin, consider alternativesReferences1. ACOG Committee on Obstetric Practice. Clinical management guidelines forobstetrician-gynecologists. Diagnosis and management of preeclampsia andeclampsia. ACOG practice bulletin. 2002;33:1-9.http://mail.ny.acog.org/website/SMIPodcast/DiagnosisMgt.pdf [cited 2012Mar 6]2. Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. Theclassification and diagnosis of the hypertensive disorders of pregnancy:statement from the International Society for the Study of Hypertension inPregnancy (ISSHP). Hypertens Pregnancy 2001;20:IX-XIV.3. Lowe SA, Brown MA, Dekker GA, Gatt S, McLintock CK, McMahon LP, et al.Guidelines for the management of hypertensive disorders of pregnancy 2008.Aust N Z J Obstet Gynaecol 2009;49:242-6.4. Australian Medicines Handbook. Adelaide: AMH; 2010.5. Sarathi V, Lila AR, Bandgar TR, Menon PS, Shah NS. Pheochromocytoma andpregnancy: a rare but dangerous combination. Endocr Pract 2010;16:300-9.6. Milne F, Redman C, Walker J, Baker P, Bradley J, Cooper C, et al. Thepre-eclampsia community guideline (PRECOG): how to screen for and detectonset of pre-eclampsia in the community. BMJ 2005;330:576-80.7. Heard AR, Dekker GA, Chan A, Jacobs DJ, Vreeburg SA, Priest KR.Hypertension during pregnancy in South Australia, part 1: pregnancyoutcomes. Aust N Z J Obstet Gynaecol 2004;44:404-9.8. Sibai BM. Magnesium sulfate prophylaxis in preeclampsia: evidence fromrandomized trials. Clin Obstet Gynecol 2005;48:478-88.9. Meher S, Abalos E, Carroli G. Bed rest with or without hospitalisationfor hypertension during pregnancy. Cochrane Database Syst Rev2005;19:CD003514.10. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk ofcardiovascular disease and cancer in later life: systematic review andmeta-analysis. BMJ 2007;335:974.11. Vikse BE, Irgens LM, Leivestad T, Skjaerven R, Iversen BM. Preeclampsia andthe risk of end-stage renal disease. N Engl J Med 2008;359:800-9.12. Levine RJ, Vatten LJ, Horowitz GL, Qian C, Romundstad PR, Yu KF, et al.Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reducedthyroid function: nested case-control and population based study. BMJ2009;339:b4336.Further readingNelson-Piercy C. Handbook of Obstetric Medicine. 4th ed. London: Royal Collegeof Obstetricians and Gynaecologists; 2010.50Full text free online at www.australianprescriber.com