Mean arterial pressure and prediction of pre-eclampsia

Abstract

Is better than diastolic or systolic pressures in low risk women, but is still only moderately effective

Pregnancies complicated by pre-eclampsia, chronic hypertension, or both, are at significantly increased risk of adverse outcomes. For most women, the assessment of blood pressure and urinalysis form the mainstay of routine antenatal care. In the recently published report by the Confidential Enquiry into Maternal and Child Health (CEMACH), pre-eclampsia or eclampsia was the second most common cause of direct maternal mortality in the United Kingdom between 2003 and 2005.¹ Although no intervention has been proved to prevent pre-eclampsia, much attention in recent years has focused on improving our ability to predict this common complication.

The accompanying meta-analysis by Cnossen and colleagues examines the relation between early pregnancy blood pressure values and subsequent development of pre-eclampsia.² In low risk women, mean arterial pressure in the second trimester was a better predictor of pre-eclampsia than systolic blood pressure or diastolic blood pressure. The predictive strength of mean arterial pressure was moderate (area under the receiver operating characteristic curve 0.76), however. The positive and negative likelihood ratios of a second trimester mean arterial pressure of ≥90 mm Hg were 3.5 and 0.46. Increases in systolic blood pressure and diastolic blood pressure over baseline showed poor predictive accuracy. The best predictor of pre-eclampsia in a widely defined “high risk” group was a diastolic blood pressure ≥75 mm Hg at 13-20 weeks’ gestation, although the predictive value was limited (positive likelihood ratio 2.8, negative likelihood ratio 0.39).

Pre-pregnancy and antenatal risk assessments are the most widely used and simplest means of predicting subsequent pre-eclampsia. Although taking a careful family history and medical history (for obstetric events, hypertension, renal disease, or thrombophilia) can help to stratify the risk of hypertensive disorders of pregnancy, history alone will identify fewer than half the women who later develop pre-eclampsia.³ Doppler ultrasonography of the uterine arteries at 20-24 weeks’ gestation, to detect abnormal trophoblast invasion, predicts about 40% of subsequent pre-eclampsia, although its success in predicting severe early onset pre-eclampsia approaches 80%.³ Recently, several predictive biochemical markers—including placental growth factor, soluble fms-like tyrosine kinase-1 (sFlt-1), plasma protein 13, and pregnancy associated plasma protein-A (PAPP-A)—have been evaluated, but none is currently in routine clinical use.⁴

Several measurements of blood pressure—including systolic blood pressure, diastolic blood pressure, pulse, mean arterial pressure, and 24 hour ambulatory pressure—have been studied in early pregnancy as predictors of pre-eclampsia.⁵ In Cnossen and colleagues’ meta-analysis, mid-trimester mean arterial pressure was the best predictor of pre-eclampsia in low risk women, but—as the authors concede—the low positive likelihood ratio makes it unlikely that this measure would have a clinical effect in isolation.² Furthermore, the ability of blood pressure measurements in early pregnancy to predict severe pre-eclampsia, which has the highest attendant risk of fetal growth restriction and perinatal mortality, was limited.

Traditionally, the criteria used to define pre-eclampsia have lacked consistency and have overemphasised diastolic blood pressure. This is because, historically, systolic blood pressure has been thought to be very variable in pregnancy.⁶ However, awareness of the importance of systolic blood pressure in pregnancy has improved, and currently both the International Society for the Study of Hypertension in Pregnancy and the working group of the national high blood pressure education program in the United States define pre-eclampsia as either systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, with associated proteinuria after 20 weeks’ gestation.^{7 8} Proteinuria is usually detected with urine dipstick testing and confirmed by a 24 hour collection. A recent review in the BMJ of spot protein:creatinine ratios in pregnancy found this to be a reasonable “rule-out” test, although 24 hour testing should still be used to accurately measure proteinuria.⁹ Diastolic only thresholds are still recommended for diagnosis in the community in the UK; this may be reasonable for pragmatic reasons, to avoid confusion arising from multiple end points.¹⁰

A clear distinction must be made between diagnostic and treatment thresholds. Anecdotally, hospital based midwifery and medical staff tend to reference only the diastolic blood pressure (“her blood pressure is on 90”), even in treatment decisions in patients with established pre-eclampsia. This trend is supported by findings from the CEMACH report and surveys of UK obstetric practice.^{1 11} Increasingly, automated blood pressure devices are being used in pre-eclampsia, and these devices may underestimate systolic blood pressure and overestimate diastolic blood pressure.¹² As such, many authorities recommend using the mean arterial pressure in severe pre-eclampsia protocols, with 125 mm Hg being the most commonly used cut-off point.

Stroke is a catastrophic, albeit relatively infrequent, complication of hypertensive disorders of pregnancy. However, intracranial haemorrhage—the biggest cause of death in women who die from pre-eclampsia or eclampsia—has been rising, not falling, in recent years.¹ The single major failing in clinical care of pre-eclampsia according to CEMACH is inadequate treatment of systolic hypertension.¹ In a recent review of haemorrhagic stroke in pregnancy, systolic blood pressure was ≥160 mm Hg immediately before the event in 96% of cases.¹³ In contrast, only 21% and 13% of patients had pre-stroke diastolic blood pressures of ≥105 mm Hg and ≥110 mm Hg. Thus, life threatening intracranial haemorrhage can occur despite only modest increases in diastolic blood pressure.

The most effective and clinically useful method to predict subsequent pre-eclampsia continues to evolve using historical, clinical, biophysical, and biochemical modalities. Early pregnancy mean arterial pressure measurements are simple to do and can be done in both community and hospital settings, but with only a modest predictive ability. A more comprehensive model of treating pre-eclampsia is needed, as are increased awareness and consistent reporting of systolic hypertension and appropriate management of both systolic blood pressure and diastolic blood pressure.