The benefits/risks of treatment of non-severe hypertension in pregnancy and choice of drug remain unanswered.

Abstract

Pregnancies complicated by non-severe hypertension are at increased risk of multiple maternal and fetal complications, such as pre-eclampsia and severe hypertension. The optimal target blood pressure achieved during pregnancy must aim for the safety of the mother and delivery of a live infant, while minimising prolonged or intensive neonatal care. Thus, one must balance the potential immediate maternal benefits against possible short- and long-term risks to the fetus and infant from the effects that lowering blood pressure have on fetal growth. Tight blood pressure control results in more women requiring antihypertensive drugs but less women developing severe hypertension, and tight blood pressure control may lead to more infants born small for gestational age (SGA). The Control of Hypertension in Pregnancy Study (CHIPS) evaluated the benefits and risks of tight versus less tight blood pressure control in women with non-severe chronic (CHTN) or gestational hypertension (GHTN) enrolled at 14–33 weeks of gestation. The primary outcome was pregnancy loss or high-level neonatal care for longer than 48 hours. Secondary outcomes were a composite of adverse maternal outcomes and rates of severe hypertension, pre-eclampsia, and SGA. There were no differences between groups in rates of either primary or secondary outcomes, pre-eclampsia, or SGA; however, severe hypertension was higher with less tight control (40.6 versus 27.5%; adjusted odds ratio, aOR 1.8; 95% confidence interval, 95% CI 1.34–2.38). Similar findings were found with CHTN, with the rate of severe hypertension being lower under tight control (43.1 versus 26.4%; aOR 0.47, 95% CI 0.34–0.65). In contrast, CHTN in the tight-control group had higher rates of SGA (19.7 versus 13.9%; OR 1.5, 95% CI 1.0–2.3). The objective of the secondary analysis from CHIPS was to determine whether the differences in outcomes between less tight and tight control of blood pressure depended on the use of labetalol or methyldopa. Analysis was performed both at and after randomisation. Mixed-effects logistic regression was used to assess the dependence of treatment on antihypertensive therapy after randomisation (labetalol or methyldopa), adjusting for factors that might influence the outcome. The analysis revealed that outcomes were not dependent on the use of labetalol or methyldopa. Based on the results of this analysis, the authors suggest that clinicians can use either agent to treat non-severe hypertension in women with CHTN or GHTN. The results of CHIPS and this secondary analysis warrant several comments. First, the statement that less tight control in CHIPS was associated with no perinatal benefit is questionable, as the trial was not powered to evaluate the effects of tight blood pressure control on the rate of SGA infants. Indeed, the rate of SGA was significantly higher with tight control in women with CHTN. Second, in women with GHTN, only 45 received labetalol and 21 received methyldopa (12 with less tight control and nine with tight control) at randomisation, and only 37 women (12 with less tight control and 25 with tight control) received methyldopa after randomisation. Thus, this analysis did not have adequate power to answer the question of whether the results in women with GHTN were modified by methyldopa or labetalol. Other studies have found labetalol to be advantageous (El-Qarmalawi et al. Int J Gynecol Obstet 1995;49:125–30; Molvi et al. Arch Gynecol Obstet 2012;285:1553–62). Third, in women with CHTN, only 47% were enrolled before 21 weeks of gestation. Moreover, there was a lack of data regarding blood pressure values at first prenatal visit, when antihypertensive medications were started, when they escalated, and the doses used. Thus, the findings may not be fully generalisable to women with CHTN seen before 20 weeks of gestation. Fourth, the use of either labetalol or methyldopa was not randomized, and the number of subjects analysed was not adequate to answer the question of whether tight control of blood pressure in women with non-severe CHTN is associated with adverse outcomes such as SGA, abruption, or indicated preterm birth, which may be related to blood pressure level achieved during treatment or to the drug used. Consequently, the results from CHIPS and the present secondary analysis did not adequately answer the above questions. Practitioners may choose not to incorporate the findings into clinical practice. Additional well-powered studies are needed to address this issue in women with GHTN or with CHTN. A large multicentre study in 4500–5500 women with CHTN enrolled at before 18 weeks of gestation is underway in the USA (Clinicaltrials.gov NCT02299414). Full disclosure of interests available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.