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Treatment > CHIPS (Control of Hypertension In Pregnancy Study)

Control of Hypertension In Pregnancy Study

Update on 28 January 2015: The CHIPS Trial results are now published in the NEJMRead more.


In the CHIPS Trial, the investigators seek to determine whether ‘less tight’ control (aiming for a diastolic blood pressure [dBP] of 100 mmHg), compared with ‘tight’ control (aiming for a diastolic blood pressure [dBP] of 85 mmHg) can decrease the risks of adverse baby outcomes without increasing the risk of problems for the mothe


Women with non-severe non-proteinuric pre-existing or gestational hypertension remote from term are a high-risk group. It is unclear how best to manage their hypertension to do more good than harm. Allowing blood pressure to be higher might improve uteroplacental perfusion, fetal growth, and ultimately, neonatal wellbeing. Based on meta-analyses of randomised trials, less tight control might decrease the risk of small-for-gestational-age infants, but may increase the risk of (transient) severe maternal hypertension, antenatal hospitalisation, and proteinuria at delivery. However, there is insufficient evidence on which to base clinical decisions because of reporting bias and between-trial heterogeneity in outcome. Guidelines are founded mainly on expert opinion. We need a definitive randomised trial to inform clinical decision-making.

Control of Hypertension In Pregnancy Study (CHIPS) is an open, multicentre, international, randomised controlled trial with an intention-to-treat analysis. The study is pragmatic: it will be undertaken to reflect real clinical practice rather than the very tightly controlled circumstances of explanatory trials. The pragmatic approach is important in this trial, where the interventions are policies of ‘less tight’ and ‘tight’ control, and it is not possible to blind clinicians or patients to the dBP goals of each treatment group.


To determine whether, for pregnant women with non-severe non-proteinuric maternal hypertension at 14-33 weeks' gestation, will less tight control (target diastolic blood pressure 100 mm Hg) compared with tight control (target diastolic blood pressure 85 mm Hg) increase or decrease the likelihood of pregnancy loss or high-level neonatal care for more than 48 h, or serious maternal complications?



CHIPS is an international multicentre randomised trial of 1028 women (514 per group) from 50 tertiary and community centres (2009-13). Eligible women will be randomised centrally to either less tight or tight control of their hypertension. Randomisation will be stratified by centre and type of hypertension. In the less tight control group, if diastolic blood pressure is 105 mm Hg or higher, antihypertensive drugs must be started or increased in dose. In the tight control group, if diastolic blood pressure is 80 mm Hg or lower, antihypertensives must be decreased in dose or discontinued. For both groups, centres will provide their usual care. Data will be collected on potential co-interventions (eg, bed-rest).


Inclusion criteria are: pre-existing/gestational hypertension; office diastolic blood pressure 90-105 mm Hg (or 85-105 mm Hg if on antihypertensives); live fetus; and 14-33 weeks' gestation. Exclusion criteria are: severe systolic hypertension (≥160 mm Hg); proteinuria; contraindication to either group of the trial or to prolongation of pregnancy; use of an angiotensin-converting-enzyme inhibitor at or after 14 weeks' gestation; known multiple gestation; lethal/major fetal anomaly; plan to terminate pregnancy; or previous participation in CHIPS.


The primary outcome is pregnancy loss (miscarriage, ectopic pregnancy, pregnancy termination, stillbirth, or neonatal death) or high-level neonatal care for 48 hr or longer in the first 28 days of life or before primary hospital discharge, whichever is later. The secondary outcome is one or more serious maternal complication(s) until 6 weeks' postpartum. Other outcomes include compliance with interventions within 4 weeks after randomisation. Women will be contacted 6-12 weeks after delivery (or loss) and, for preterm babies, when the baby is at 36 weeks' corrected postgestational-age to inquire about satisfaction with care and any major maternal/neonatal morbidity after hospital discharge.

Analysis plan

The primary outcome will be compared between groups with multivariate logistic regression (α = 0·046, two-sided). We have based our sample size on a clinically important reduction in pregnancy loss or high-level neonatal care for more than 48 h from 33% to 25%. Two interim analyses are planned after primary outcome data are available for one-third and then two-thirds of enrolled women. An independent data and safety monitoring board will consider early termination of the trial at the first and second interim analyses, with a two-tailed test of significance at the p<0·0002 and p<0·012 levels, respectively.


The CHIPS study is now published in the NEJM. Read more here


  • Further CHIPS analyses: The impact on outcome of both BP level and variability will be explored, in an effort to fully understand the predictive power of BP, as well as an overview paper is planned.
  • CHIPS-Child: In this follow-up study of CHIPS, the developmental programming hypothesis is being tested by determining if children born of mothers in ‘less tight’ (vs. ‘tight’) BP control arms of CHIPS showed differences in postnatal growth and health. The results were presented in October 2016 at the International Society for the Study of Hypertension in Pregnancy (ISSHP) meeting, Brazil.
  • CHIPS implementation: The next steps will be to further our understanding of the views about ‘tight’ and ‘less tight’ control of BP, and undertake implementation planning in low- and middle-income countries (LMICs). The views of women will be explored with regards to the choices that they would make for BP control and why. The views of clinicians will be also be explored in a formal stakeholder analysis planned for 2017-8.Furthermore, we will work towards implementation of a ‘tight’ BP control target in LMICs, using methyldopa as the antihypertensive. This is particularly important in under-resourced settings where maternal surveillance is less available and less frequent, whether that surveillance is delivered by the women through home BP (and other) monitoring, by community health workers at home, in primary health centres (PHCs), or by clinicians at PHCs or facilities