Chronic Hypertension in Pregnancy Dr. M. Barekat February 2013 Bushehr-Iran

n engl j med 365;5 nejm.org august 4, 2011 Dr.M.Barekat 2/17/2019

Dr.M.Barekat 2/17/2019

Dr.M.Barekat 2/17/2019

National Institute for Health and Clinical Excellence(NICE) Dr.M.Barekat 2/17/2019

Dr.M.Barekat 2/17/2019

Alabama Perinatal Excellence Collaborative 10/17/2012 Dr.M.Barekat 2/17/2019

Dr.M.Barekat 2/17/2019

Dr.M.Barekat 2/17/2019

The Journal of Lancaster General Hospital • Fall 2008 • Dr.M.Barekat 2/17/2019

Classification of Hypertension in Pregnancy Dr.M.Barekat 2/17/2019

Incidance HTN occurs in up to 22% of women of childbearing age 1% of pregnancies are complicated by chronic hypertension 5-6% by gestational hypertension (without proteinuria) 1-2% by preeclampsia. Dr.M.Barekat 2/17/2019

Definition BP of at least 140 mm Hg systolic or 90 mm Hg diastolic pressure before pregnancy or For women who first present for care during pregnancy, before 20 weeks of gestation Or persistent after 12 weeks’ postpartum Dr.M.Barekat 2/17/2019

Grading Mild (140–159/90–109 mmHg) Severe (≥160/ 110 mmHg) Dr.M.Barekat 2/17/2019

Prevalence As high as 3% Primarily attributable to Increased prevalence of obesity Delayed childbearing Dr.M.Barekat 2/17/2019

Complications Most have good pregnancy outcomes Increased frequency of preeclampsia (17 to 25%, vs. 3 to 5% in the general population) Placental abruption two times more(1.56% vs. 0.58%) and even more if associated with preeclampsia Fetal growth restriction (SGA), specially when associated with preeclampsia(10 to 20% and even 50% in a Danish report) Preterm birth Cesarean section The risk of superimposed preeclampsia increases with an increasing duration of hypertension Dr.M.Barekat 2/17/2019

Clinical course Most have a decrease in BP during pregnancy, similar to that observed in normotensive women BP falls toward the end of the first trimester and rises toward prepregnancy values during the third trimester As a result, antihypertensive medications can often be tapered 7 to 20% of women have worsening of hypertension during pregnancy without the development of preeclampsia Dr.M.Barekat 2/17/2019

Prepregnancy Evaluation Assessment of target-organ damage Blood glucose, hematocrit, serum potassium, creatinine, calcium, and lipoprotein profile, as well as urinalysis ECG 24-hour quantification of urine protein to facilitate the identification of subsequent superimposed preeclampsia The presence of end-organ manifestations of hypertension may worsen the prognosis Dr.M.Barekat 2/17/2019

Prepregnancy Evaluation The evaluation of identifiable causes of hypertension is generally limited to women with hypertension that is resistant to therapy or that requires multiple medications or to those who have symptoms or signs that suggest a secondary cause Dr.M.Barekat 2/17/2019

Monitoring for Preeclampsia Superimposed preeclampsia should always be considered when the blood pressure increases in pregnancy or when there is a new onset of or an increase in baseline proteinuria An elevated uric acid level may help to distinguish the two conditions (some overlaps) Presence of thrombocytopenia or elevated values on liver-function testing may also support a diagnosis of preeclampsia Dr.M.Barekat 2/17/2019

Goal Of Therapy A primary reason for treating hypertension in pregnancy is to reduce maternal morbidity Meta-analysis including 28 randomized trials comparing antihypertensive treatment either with placebo or with no treatment showed that: Antihypertensive treatment significantly reduced the risk of severe hypertension. However, treatment did not reduce: Risks of superimposed preeclampsia Placental abruption Growth restriction Nor did it improve neonatal outcomes Dr.M.Barekat 2/17/2019

Antihypertensive Medications The only trial of treatment of hypertension in pregnancy with adequate infant follow-up (7.5 years) was performed years ago with a-methyldopa No adverse developmental effect Dr.M.Barekat 2/17/2019

Antihypertensive Medications Methyldopa is considered to be a first-line therapy in pregnancy by many guidelines Frequently causes somnolence, which may limit its tolerability Adult Dose: 250 mg PO bid/tid; increase q2d prn; not to exceed 3 g/d. Contraindications: acute liver disease Dr.M.Barekat 2/17/2019

Beta-blockers Use of beta-blockers resulted in fewer episodes of severe hypertension than the use of methyldopa Labetalol, a combined alpha- and beta-receptor blocker, is often recommended as another first-line or second-line therapy 200-400mg/day in 2-3 divided doses Association between atenolol and fetal growth restriction Not been reported with the use of other beta-blockers or labetalol Dr.M.Barekat 2/17/2019

Other Antihypertensive Medications Long-acting calcium-channel blockers also appear to be safe in pregnancy, although experience is more limited than with labetalol Diuretics were long considered contraindicated in pregnancy because of concern about volume depletion Review of nine randomized trials showed no significant difference in pregnancy outcomes continuation of diuretic therapy during pregnancy Dr.M.Barekat 2/17/2019

The only drugs that are contraindicated First trimester exposure: Angiotensin-converting–enzyme inhibitors and angiotensin-receptor blockers The only drugs that are contraindicated First trimester exposure: Potential teratogenic effects including cardiovascular and CNS defects Second half of pregnancy exposure: Oligohydramnios (probably resulting from impaired fetal renal function) and neonatal anuria and renal failure, growth abnormalities, skull hypoplasia, and fetal death Dr.M.Barekat 2/17/2019

Lifestyle modifications Weight reduction and increased physical activity, have been shown to improve BP control in nonpregnant women The American College of Obstetrics and Gynecology recommends weight reduction before pregnancy in obese women However, data are lacking to inform whether such measures improve pregnancy outcomes specifically in women with hypertension Normal diet without salt restriction is advised, particularly close to delivery, as salt restriction may induce low intravascular volume Dr.M.Barekat 2/17/2019

Blood-Pressure Goals in Pregnancy Various professional guidelines provide disparate recommendations regarding indications for starting therapy (ranging from a blood pressure of >159/89 mm Hg to one of >169/109 mm Hg) and for blood-pressure targets for women who are receiving therapy (ranging from <140/90 mm Hg to <160/110 mm Hg). Our recommendation: start medication with BP>169/109 and keep it<150/100 Dr.M.Barekat 2/17/2019

Starting Medical RX Medscape, Feb 24, 2012: SBP >160 mm Hg or the DBP >100-105 mmHg. Braunwald 2012: Only if diastolic pressures remain above 100 mm Hg Royal College of OB and GYN 2011: BP>150/100 ESC Guidelines 2011:SBP 150> mmHg and a DBP > 95 mmHg. Dr.M.Barekat 2/17/2019

Blood-Pressure Goals in Pregnancy Some experts recommend stopping antihypertensive agents during pregnancy, as long as blood pressures fall below such thresholds. Meta-analysis showed greater magnitude of blood pressure lowering was associated with an increased risk of fetal growth restriction So prepregnancy doses of antihypertensive agents may need to be reduced, particularly in the second trimester Dr.M.Barekat 2/17/2019

Prevention of Preeclampsia No significant reduction in the risk of preeclampsia associated with the use of low-dose aspirin, calcium supplementation, or antioxidant supplementation with vitamins C and E Although antihypertensive medications are effective in treating chronic hypertension that has worsened during pregnancy, they are not effective in preventing preeclampsia Dr.M.Barekat 2/17/2019

NICE Guidelines on hypertension in Pregnancy January 2011 Dr.M.Barekat 2/17/2019

Fetal Surveillance More frequent prenatal visits Measuring blood pressure and urine protein Evaluation of fetal growth Regular evaluation of fundal height with ultrasonographic estimation of fetal weight, beginning in the early third trimester and continuing at intervals of 2 to 4 weeks Dr.M.Barekat 2/17/2019

Time of Delivery Weigh the risks of fetal morbidity associated with delivery before term against the risks of maternal and fetal complications from continued expectant management At 39 weeks and no later than 40 weeks Not before 37 weeks if BP<160/110 mmHg, with or without antihypertensive treatment Dr.M.Barekat 2/17/2019

Breast-feeding Breast-feeding should be encouraged Although most antihypertensive agents can be detected in breast milk, levels are generally lower than those in maternal plasma Most antihypertensive agents, including ACE inhibitors, as “usually compatible” with breast-feeding Data are lacking with respect to the use of ARBs and breast-feeding Dr.M.Barekat 2/17/2019

Breast-feeding Case reports have described lethargy and bradycardia in newborns who are breast-fed by mothers taking atenolol No such cautions are noted for other beta-blockers, such as metoprolol Use of long-acting nifedipine, labetalol, methyldopa, captopril, and enalapril is acceptable during breastfeeding Dr.M.Barekat 2/17/2019

Postpartum Careful monitoring for at least 48h after delivery as they are at increased risk of renal failure , pulmonary edema and hypertensive encephalopathy Measure blood pressure: Daily for the first 2 days after birth At least once between day 3 and day 5 after birth As clinically indicated if antihypertensive treatment is changed after birth Dr.M.Barekat 2/17/2019

Postpartum Continue antenatal antihypertensive treatment. Review long-term antihypertensive treatment 2 weeks after the birth. If a woman has taken methyldopa to treat chronic hypertension during pregnancy, stop within 2 days of birth because of the risk of post-natal depression and restart appropriate antihypertensive treatment Dr.M.Barekat 2/17/2019

Areas of Uncertainty Whether women with mild-to-moderate hypertension should receive antihypertensive treatment which target blood pressure should be used for treatment Which antihypertensive agents are superior Dr.M.Barekat 2/17/2019

Take home message primary reason for treating hypertension in pregnancy is to reduce maternal morbidity Before attempting to conceive, the patient should replace the ACE inhibitor (methyldopa, labetalol, or a long-acting calcium-channel blocker prepregnancy doses of antihypertensive agents may need to be reduced, particularly in the second trimester Dr.M.Barekat 2/17/2019

Take home message Although some guidelines recommend the first-line use of methyldopa on the basis of its long safety record, we would generally use labetalol first Start medication with BP>169/109 Adjust medications to maintain blood pressure between 130/80 mm Hg and 150/100 mm Hg Dr.M.Barekat 2/17/2019

Thank you for attention Dr.M.Barekat 2/17/2019