ACOG task force on hypertension in pregnancy--A step forward in management

You have just admitted a previously healthy nullipara at 36 weeks’ gestation who presented with new-onset periorbital edema and is found to have blood pressure readings of 150/100 to 155/105 mmHg, 4+ protein on urinary dipstick, modest (ie, less than 2-fold) elevations in her hepatic transaminases, a platelet count of 105,000/µL and a mildly (8th percentile) growth-restricted fetus. Does she have severe preeclampsia? Should you start parenteral magnesium sulfate? Should you give antihypertensive therapy? Is delivery indicated?

According to a new report from the American College of Obstetricians and Gynecologists (ACOG) Task Force on Hypertension in Pregnancy, the answer to all these questions is no. On balance, the Task Force provides much-needed updating of our thinking about this ancient disease and provides concise, lucid, and contemporary management strategies. However, as this case presentation indicates, the report’s recommendations will not be free of controversy.

Preeclampsia: Magnitude and management

Hypertensive disorders complicate 5% to 10% of pregnancies, whereas preeclampsia occurs in about 3% of pregnancies in industrialized nations.¹ Hypertensive disorders account for 5% to 10% of maternal deaths in the developed world.^2,3 Rates of perinatal mortality are also increased 2- to 3-fold in hypertensive mothers, and women with early-onset preeclampsia have a 4-fold increased risk of stillbirth.^1,4 Ironically, severe preeclampsia is a major risk factor (80-fold increase) for iatrogenic early preterm birth, yet preterm infants of preeclamptic mothers have lower rates of perinatal mortality than gestational-age-matched preterm infants of normotensive mothers.¹ This may reflect the benefits of “stress” among the former and the effects of infection among the latter cases. On the other hand, it has now been well established that mothers with the disorder are at increased risk of cardiovascular disease later in life.^5,6

Agreement is universal that only delivery “cures” the disease, but preeclampsia poses many definitional and management dilemmas. In preterm cases we must balance the risks to the mother of expectant management against the potential benefits to the fetus. The relative prognostic importance of the severity of proteinuria is another point of contention. Ongoing debate about the use of parenteral magnesium sulfate in non-severe cases is particularly fierce. Finally, strategies to prevent the long-term cardiovascular mortality accruing affected mothers remain enigmatic.

Task force recommendations

The Task Force recommendations are far-reaching and address many of the clinical diagnostic and management conundrums described above.⁷ The Task Force consisted of 17 experts in the field who graded available evidence to better define the disorder and optimize management. One key conclusion was to abandon the requirement that proteinuria be present to confirm the diagnosis. This decision reflects our growing understanding that the disease affects multiple organ systems and that renal involvement is not required for attendant maternal and perinatal morbidity and mortality.

The Task Force suggests that the diagnostic criteria for preeclampsia be changed to include the usual hypertensive thresholds (ie, systolic and diastolic blood pressures ≥140 and ≥90 mm Hg, respectively, occurring twice, 4 hours apart, after 20 weeks) with either proteinuria (ie, ≥300 mg per 24 hours, protein to creatinine ratio ≥0.3 day or 1+ urinary protein dipstick reading) or, in the absence of proteinuria, new onset of any of the following systemic findings: a) thrombocytopenia (platelet counts <100,000 µL); b) renal insufficiency (ie, creatinine >1.1 mg/dL or 2-fold increase in creatinine in the absence of underlying renal disease); c) abnormal liver function (ie, hepatic transaminase levels twice normal); d) pulmonary edema; or e) cerebral or visual symptoms.

Similarly, eliminated from measures of severe preeclampsia are massive proteinuria (ie, >5 g/day) and fetal growth restriction because the extent of proteinuria does not predict morbidity, and fetal growth restriction occurs commonly in the absence of associated preeclampsia. The new definition of severe preeclampsia includes any of the following: 1) systolic or diastolic blood pressures values ≥160 or 110 mm Hg, respectively, occurring twice, 4 hours apart at bed rest; 2) thrombocytopenia (platelet counts <100,000 µL); 3) impaired liver function defined as either otherwise unexplained right-upper-quadrant-epigastric pain unresponsive to medications, or hepatic transaminase levels twice normal; 4) progressive renal insufficiency as defined above; 5) pulmonary edema; and 6) new-onset cerebral or visual disturbances. One assumes that findings 2–6, if isolated, must occur in the setting of hypertension because other disorders (such as gestational thrombocytopenia, hepatitis, acute tubular necrosis, peripartum cardiomyopathy, and new-onset migraine) can present with these isolated “severe features.” Obviously the combination of hepatic dysfunction and thrombocytopenia with hemolysis still constitutes HELLP syndrome (so named because it involves hemolysis, elevated liver enzymes, and a low platelet count).

The classification of the other 3 hypertensive disorders in pregnancy remains unchanged, including: gestational hypertension defined as new onset of threshold blood pressure elevations after 20 weeks’ gestation; chronic hypertension wherein such blood pressure elevations predate pregnancy; and superimposed preeclampsia (ie, chronic hypertension in association with preeclampsia).

The key management recommendations include eliminating the requirements for bed rest, delivery prior to 37 0/7 weeks’ gestation, and antihypertensive therapy or intrapartum magnesium sulfate for patients with mild gestational hypertension and non-severe preeclampsia. Thus, the patient I described in the first paragraph would not be delivered, would not be prescribed bed rest or antihypertensive therapy, and would not be treated with magnesium sulfate. I suspect a number of our readers might take issue with a few of these positions!

Recommendations for severe preeclampsia including HELLP syndrome are less controversial. Delivery after stabilization is still recommended for severe preeclamptic patients with onset at or after 34 0/7 weeks and those with unstable maternal and fetal conditions at any gestational age. Similarly, onset before viability should prompt immediate delivery. For affected patients between 24 and 34 weeks’ gestation, recommendations include antenatal corticosteroids, transfer to a tertiary care facility, and antihypertensive therapy if blood pressures reach or exceed 160/110 mm Hg. Delivery of these preterm patients after the 48-hour corticosteroid window would be indicated with any of the following: preterm premature rupture of the membranes, labor, persistently abnormal (≥2-fold increase) transaminase elevations, platelet count <100,000/µL, fetal growth restriction <5th percentile, and severe oligohydramnios (ie, AFI <5 cm) absent end-diastolic umbilical artery Doppler flow studies and new-onset renal dysfunction.

The Task Force also makes the apparently contradictory recommendation that “corticosteroids be given” in such severely affected patients at less than 34 weeks’ gestation, but that “delivery not be delayed after initial stabilization” if there is uncontrollable severe hypertension, eclampsia, pulmonary edema, abruption, disseminated intravascular coagulation, nonreassuring fetal status, or intrapartum fetal demise. I assume the committee members intended that steroids should be started but delivery expedited if any of these conditions subsequently develop in the next 48 hours.

The Task Force does still recommend parenteral magnesium sulfate therapy in cases of eclampsia and during the intrapartum period for patients with severe preeclampsia. Such therapy should also be administered intraoperatively if a cesarean delivery is indicated. They also recommend magnesium sulfate for women with new-onset hypertension accompanied by headaches, visual changes, or severe features in the postpartum period. The cutoff for antihypertensive therapy in the postpartum period is 150/100 mm Hg present on 2 occasions, 4–6 hours apart.

The Task Force endorses observing blood pressures in postpartum patients with gestational hypertension, preeclampsia, and superimposed preeclampsia for 72 hours in hospital and after 7 to 10 days postpartum. They recommend using low-dose aspirin for prophylaxis in pregnant women with prior preterm preeclampsia or 2 or more previously affected pregnancies. For pregnant chronic hypertensive patients, therapy with labetalol, nifedipine, or methyldopa is recommended for systolic blood pressures ≥160 mm Hg or diastolic pressures ≥105 mm Hg or with lower levels of hypertension if there is evidence of end-organ damage. Finally, they make common-sense-though non-evidence-based-recommendations that women with a history of preeclampsia lose weight, exercise, not smoke and have their blood pressure, fasting glucose, and lipid levels followed yearly to mitigate their risks of subsequent cardiovascular mortality.

Take-home message

The ACOG Task Force on Hypertension in Pregnancy has made evidence-based recommendations to modernize the definition and management of preeclampsia. Eliminating proteinuria as a requisite for the diagnosis of severe and non-severe forms of the disorder is warranted. Furthermore, many of their management recommendations, particularly those for severe disease, provide much-needed clarity.

While I appreciate the basis of the Task Force’s strong stand for withholding intrapartum magnesium sulfate therapy in patients with non-severe forms of the disease, I cannot agree with it. Although it had limitations, the original MAGPIE randomized control trial of magnesium sulfate therapy versus placebo in preeclamptic patients found that treatment lowered the risk of eclampsia by 58% (relative risk [RR] 0.42; 95% CI, 0.29–0.60), reduced maternal mortality rates (RR 0.55, 95% CI, 0.26–1.14), and decreased the occurrence of abruption (RR 0.67, 99% CI, 0.45–0.89).⁸ For non-severe cases, the number needed to treat to prevent 1 eclamptic episode was 109 (95% CI, 72–225).

A recent Cochrane review also confirms the efficacy of magnesium sulfate in preventing eclampsia among patients with non-severe disease (RR 0.44, 95% CI, 0.28–0.69) with a number needed to treat of 100.⁹  Such therapy significantly reduces the risk of abruption (RR 0.64, 95% CI, 0.5–0.83) also with a number needed to treat of 100. Thus, the decision to use magnesium sulfate to treat patients with non-severe preeclampsia is ultimately a judgment call wherein the costs and side effects of treatment must be weighed against the low but not rare risks of seizures, abruption, and even maternal mortality. Despite this reservation, on balance, the Task Force report should improve the clinical management of pregnant patients with hypertensive disorders.

Dr. Lockwood, editor in chief, is Dean of the College of Medicine and Vice President for Health Sciences at The Ohio State University, Columbus, Ohio.

References

1. Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol. 2011;25(4):391–403.

2. Campbell KH, Savitz D, Werner EF, et al. Maternal morbidity and risk of death at delivery hospitalization. Obstet Gynecol. 2013;122(3):627-633.

3. Saucedo M, Deneux-Tharaux C, Bouvier-Colle MH; French National Experts Committee on Maternal Mortality. Ten years of confidential inquiries into maternal deaths in France, 1998-2007. Obstet Gynecol. 2013;122(4):752-760.

4. Mbah AK, Alio AP, Marty PJ, Bruder K, Whiteman VE, Salihu HM. Pre-eclampsia in the first pregnancy and subsequent risk of stillbirth in black and white gravidas. Eur J Obstet Gynecol Reprod Biol. 2010;149(2):165–169.

5. Funai EF, Friedlander Y, Paltiel O, et al. Long-term mortality after preeclampsia. Epidemiology. 2005;16(2):206–15.

6. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007;335(7627):974.

7. American College of Obstetricians and Gynecologists. Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122–1131.

8. Altman D, Carroli G, Duley L, et al; Magpie Trial Collaboration Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet. 2002;359(9321):1877-1890.

9. Duley L, Gülmezoglu AM, Henderson-Smart DJ, Chou D. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010;(11):CD000025. doi: 10.1002/14651858.CD000025.pub2.