When should pregnant women with an elevated blood pressure be treated?

Volker Homuth, Ralf Dechend and Friedrich C. Luft

Franz Volhard Clinic, HELIOS-Klinikum Berlin, Medical Faculty of the Charité, Humboldt University of Berlin, Germany

Correspondence and offprint requests to: Volker Homuth, Franz Volhard Clinic, Wiltberg Strasse 50, D-13125 Berlin, Germany. Email: homuth{at}fvk-berlin.de

Keywords: antihypertensives; hypertension; non-target effects; pregnancy

Hypertension in pregnancy continues to be a vexing clinical problem. The dilemma is amplified by the fact that today, women are choosing to have their children later in life. At a recent symposium on hypertension and pregnancy at the German Society of Hypertension (Deutsche Liga zur Bekämpfung des hohen Blutdrucks), the authors made the statement that totally asymptomatic pregnant women with a normally developing pregnancy, who have no other concomitant medical problems, need not be treated with medications unless their blood pressure exceeds 170/110 mmHg. This statement led to some consternation in the audience and we were asked to formally defend our position on the basis of the evidence. A lively discussion also ensued regarding which of the two patients, patient 1, the mother or patient 2, the child, accrues benefit from treatment and which patient may be harmed.

Hypertension in pregnancy is a heterogeneous condition. Some women have chronic renal disease which is responsible for elevated blood pressure. Others have chronic primary hypertension. Some are normotensive prior to pregnancy and show an elevated blood pressure during pregnancy. These women are labelled as having pregnancy-induced hypertension. The term ‘gestational hypertension’ is applied if blood pressure reverts to normal after delivery. Then, there is the dreaded complication of pregnancy, namely pre-eclampsia–eclampsia. These women are normotensive prior to their pregnancies. They develop proteinuria after the 20th week, develop hypertension with blood pressure values >140/90 mmHg, commonly have oedema and may proceed to develop elevated liver enzymes and thrombocytopenia (HELLP syndrome). Pre-eclampsia is not the issue in our commentary. Its management is beyond the scope of this discussion.

Clearly, all of these hypertensive pregnant women cannot merely be thrown into one pot. Another confounding variable is the fact that the absence of past medical records, as well as sporadic or no prior medical care, may make the identification of the various forms of hypertension impossible. We are aided by two recent literature reviews. Magee et al. [1] relied on a MEDLINE search. They observed that authors commonly did not distinguish between the various causes of hypertension, including pre-eclampsia. The severity of hypertension in terms of diastolic pressure in their analysis was classified as mild (90–99 mmHg), moderate (100–109 mmHg) or severe (>=110 mmHg). The authors also noted that details on blood pressure measurements were seldom complete. They could not discern whether Korotkoff IV or V was used in the studies to determine the diastolic pressure. The endpoints in the studies were also ill defined. In their analysis, the authors concluded that antihypertensive drugs were better than no therapy in terms of avoiding the development of severe hypertension and the requirements for additional hypertensive drugs. Only one study suggested that antihypertensive treatment reduced the necessity of hospital admission before term. Decrease in proteinuria before delivery, a marker of pre-eclampsia, was a finding of borderline significance in their meta-analysis. However, the authors point out that the definition and documentation of proteinuria in the studies was haphazard, making any firm conclusions difficult. No effect was shown on perinatal outcomes. The authors concluded that treatment of chronic hypertension early in pregnancy might benefit the mother.

In terms of treating hypertension that develops later in pregnancy, the authors could find no benefit for various non-pharmacological treatments, including hospital admission [1]. The drug trials again suggested a decrease in the development of severe hypertension by treatment, a lesser eventual drug requirement and a decrease in the occurrence of proteinuria. Three perinatal effects were notable. There was a decrease in respiratory distress syndrome, more bradycardia occurred, at least in the beta-blocker trials, and there was a trend towards an increase in the incidence of small-for-gestational-age infants. The authors concluded that there was some evidence for a maternal benefit of treatment. No reliable conclusions could be made regarding perinatal outcomes. Borghi et al. [2] came to similar conclusions. They added their own data, suggesting that nifedipine GITS is superior to methyldopa and possibly other drug selections.

We believe that one major area of concern is the effect of treatment on fetal growth restriction. This topic was examined by von Dadelszen et al. [3]. They also resorted to a meta-analysis of 45 trials that allocated 3773 pregnant hypertensive women to treatment or no treatment. The authors documented a clear-cut association between blood pressure reduction and small-for-gestational-age infants. The authors raised the issue that since the maternal benefits in the studies were small or ill defined, we had better be pretty careful to avoid causing injury to patient 2!

The Working Group Report on High Blood Pressure in Pregnancy (US National Institutes of Health) issued their report in 2000 [4]. They observed that in patients with chronic hypertension already on treatment, the regimen of course must be adjusted for the pregnancy and that many centres currently stop antihypertensive treatment altogether. Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers must absolutely be discontinued. Diuretics are currently viewed with disfavour. Endpoints for reinstituting treatment include exceeding threshold blood pressure levels of 150–160 mmHg systolic and 100–110 mmHg diastolic.

The German Society of Hypertension currently recommends treatment if blood pressure exceeds 160/100 mmHg [5]. The occurrence of such values early in pregnancy suggests the presence of chronic hypertension. The development of such values late in pregnancy requires close observation. Values up to 170/110 mmHg could be tolerated without treatment if the patient is under observation in the hospital.

Clearly, we are traipsing in the dark. We have little evidence that we protect women from pre-eclampsia by treating their blood pressure during pregnancy with drugs. Trends and isolated studies are not sufficient [6], particularly when such treatment early in pregnancy might induce fetal growth retardation [7]. We need more data and more trials. Our dilemma is likely to become progressively worse as the chances of women with chronic renal disease or cardiac disorders carrying pregnancies to term improve. Until we have better data, we must satisfy ourselves with individualized treatment, including watchful waiting.

References

  1. Magee LA, Ornstein MP, von Dadelszen P. Management of hypertension in pregnancy. Br Med J 1999; 318: 1332–1336[Free Full Text]
  2. Borghi C, Esposti DD, Cassani A, Immordino V, Bovicelli L, Ambrosioni E. The treatment of hypertension in pregnancy. J Hypertension 2002; 20 [Suppl 2]: S52–S56[Medline]
  3. von Dadelszen P, Ornstein MP, Bull SB, Logan AG, Koren G, Magee LA. Fall in mean arterial blood pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis. Lancet 2000; 355: 87–92[CrossRef][ISI][Medline]
  4. Working Group on High Blood Pressure in Pregnancy, NIH publication no. 00-3029. National Institutes of Health, Bethesda, MD: 2000
  5. German Society of Hypertension (Deutsche Liga zur Bekämpfung des hohen Blutdrucks). Guidelines for the management of hypertension. Dtsch Med Wochenschr 2001; 126 [Suppl 4]: S201–S238[ISI]
  6. Rubin PC, Butters L, Clark DM et al. Placebo-controlled trial of atenolol in treatment of pregnancy-associated hypertension. Lancet 1983; 1: 431–434[Medline]
  7. Butters L, Kennedy S, Rubin PC. Atenolol in essential hypertension during pregnancy. Br Med J 1990; 301: 587–589[ISI][Medline]