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The Evidence Speaks

THE EVIDENCE SPEAKS: The Control of Hypertension in Pregnancy Study (CHIPS Trial)

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This overview is also available as an infographic.


About 10 per cent of pregnant women have high blood pressure which can either be pre-existing (chronic hypertension) or developed during pregnancy (gestational hypertension). Hypertensive disorders during pregnancy are a primary cause of death and illness in both mothers and newborns. Meta-analyses of randomized, controlled trials (RCTs) found conflicting evidence for high versus low blood pressure and the effect on neonatal health outcomes; some found that the use of antihypertensive medication during pregnancy increases the risk of low birthweight while others suggest these drugs benefit mothers. This led to the formation of the Control of Hypertension in Pregnancy Study (CHIPS) Group, which included CHÉOS Scientist Dr. Joel Singer and statistician Dr. Terry Lee.

Maternal hypertension can be tracked using diastolic blood pressure (dBP), which is the pressure exerted on the walls of the blood vessels during the relaxation phase of the cardiac cycle (diastole). The CHIPS Group set out to determine how tightly blood pressure should be controlled – using antihypertensive medications – to optimize the health of the newborn without increasing pregnancy-related complications; specifically, to compare a target dBP of 85 mmHg (tight control) versus 100 mmHg (less-tight control).

Pilot Trial

Before initiating the large trial, the CHIPS Group completed a pilot study to test whether such a trial was feasible, whether the different anti-hypertensive strategies produced meaningful differences in blood pressure, and whether the research participants would be satisfied with the care received during the trial. The results of the pilot stage showed that the interventions were successful in controlling blood pressure and there was a trend towards fewer complications in newborns in the less-tight group.1 Most importantly, there was a enough of a difference in blood pressure between the groups to justify the expectation that this could translate into differences in clinical outcomes between the groups. Analysis of questionnaire data showed that mothers in both groups were equally satisfied with the care received.2

Full trial

The full RCT, which was published in the New England Journal of Medicine in 2015, enrolled 987 pregnant women with either chronic or gestational hypertension and split them into the same treatment groups as the pilot trial. There were no significant differences between the groups when it came to risk of pregnancy loss, poor neonatal health, or maternal complications. However, mothers in the less-tight group were more likely to experience severe maternal hypertension (BP ≥ 160/110 mmHg). The RCT was conducted from 2009 to 2014 and collected data from 94 sites in 16 countries, including sites in 8 Canadian provinces.3

Participating mothers were also given a questionnaire 6 to 12 weeks after giving birth. Analysis of these data showed that women in the tight control group were equally satisfied with their care compared to the less-tight group. Interestingly, in mothers who experienced pregnancy-related complications or whose newborn had adverse health outcomes, satisfaction with care was higher in the tight group versus the less-tight group.4

Secondary Analysis

After publication of the main trial results there remained several secondary analyses needed to fully understand the data collected. It should be understood that the CHIPS trial was not designed to answer these questions, meaning that care needs to be taken when interpreting these secondary analyses.

Women in the trial could have been on an antihypertensive medication when recruited or could have been placed on one after randomization into one of the study groups. The two most commonly prescribed drugs were labetalol and methyldopa. Analysis of differences in study outcomes for less-tight versus tight control found that the type of drug had no significant impact on the CHIPS results.5 However, independent of the type of blood pressure control criteria used, methyldopa was associated with fewer health complications in both mothers and babies.6

The CHIPS team also wanted to see if it was possible to predict adverse maternal or neonatal outcomes using risk markers collected when hypertension is diagnosed. Nineteen predictor variables were measured, such as body mass index, gestational age at diagnosis, and folic acid levels, but it was not possible to predict which women were at an increased risk of adverse outcomes. Although women in the less-tight group were more likely to develop severe hypertension, the predictive modelling used in this secondary analysis was not able to identify which women in this group were at a greater risk.7 Severe hypertension was associated with poorer health in newborns in both groups. Severe hypertension was also associated with poorer maternal outcomes, but only in the less-tight group.8

The cost implications of the two hypertension management strategies were analyzed as well. Although the mean cost per mother-infant pair was roughly $6,000 more in the less-tight group, the difference was not statistically significant. The general conclusion from this cost analysis was that tight control of blood pressure during pregnancy is not more expensive from a third-party payer perspective.9

Most recently, the team explored whether gestational age at the start of antihypertensive therapy had any impact on the relationship between the study outcomes and less-tight versus tight control. Randomization to treatment only before 24 weeks to less-tight control was associated with fewer low birth weight babies, but also more preterm birth. The association between less-tight control and severe hypertension that existed at all gestational ages was strongest at gestational age before 28 weeks. Of perhaps most consequence was the finding that at no gestational age does less-tight control appear the superior management strategy.10

What did we learn?

The CHIPS trial and publications represent a fully formed analysis of data from a high-quality, international, randomized, controlled trial. What did we learn from it? We know that severe hypertension can be harmful to the health of mothers, and CHIPS showed that tight control of blood pressure during pregnancy decreases the risk of developing severe hypertension without sacrificing care satisfaction or increasing risk to newborns. Also, tight control of blood pressure likely costs the health care system less money per birth.

In the real world, pregnant women are less likely to be as closely monitored as they were during the trial. Because antihypertensive treatment doesn’t appear to harm the baby, the health of the mother should be protected by tightly controlling blood pressure using these medications.

The CHIPS trial was funded by the Canadian Institutes for Health Research, NCT01192412. This overview is also available as an infographic.


  1. Magee LA, Dadelszen von P, Chan S, et al. The Control of Hypertension In Pregnancy Study pilot trial. BJOG. 2007;114(6):770–e13–20.
  2. Magee LA, Dadelszen von P, Chan S, et al. Women’s views of their experiences in the CHIPS (Control of Hypertension in Pregnancy Study) Pilot Trial. Hypertens Pregnancy. 2007;26(4):371-387.
  3. Magee LA, Dadelszen von P, Rey E, et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015;372(5):407-417.
  4. Vidler M, Magee LA, Dadelszen von P, et al. Women’s views and postpartum follow-up in the CHIPS Trial (Control of Hypertension in Pregnancy Study). Eur J Obstet Gynecol Reprod Biol. 2016;206:105-113.
  5. Magee LA, CHIPS Study Group, Dadelszen von P, et al. Control of Hypertension In Pregnancy Study randomised controlled trial-are the results dependent on the choice of labetalol or methyldopa? BJOG. 2016;123(7):1135-1141.
  6. Magee LA, CHIPS Study Group, Dadelszen von P, et al. Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial. BJOG. 2016;123(7):1143-1151.
  7. Magee LA, Dadelszen von P, Singer J, et al. Can adverse maternal and perinatal outcomes be predicted when blood pressure becomes elevated? Secondary analyses from the CHIPS (Control of Hypertension In Pregnancy Study) randomized controlled trial. Acta Obstet Gynecol Scand. 2016;95(7):763-776.
  8. Magee LA, Dadelszen von P, Singer J, et al. The CHIPS Randomized Controlled Trial (Control of Hypertension in Pregnancy Study): Is severe hypertension just an elevated blood pressure? Hypertension. 2016 Sep 12 [epub].
  9. Ahmed RJ, Gafni A, Hutton EK, et al. The Cost Implications of Less Tight Versus Tight Control of Hypertension in Pregnancy (CHIPS Trial). Hypertension. 2016;68(4):1049-1055.
  10. Pels A, Mol BWJ, Singer J, et al. Influence of Gestational Age at Initiation of Antihypertensive Therapy: Secondary Analysis of CHIPS Trial Data (Control of Hypertension in Pregnancy Study)Hypertension. 2018 May; 71(5). Epub 2018 Apr 23.