The CHIPS Randomized Controlled Trial (Control of Hypertension in Pregnancy Study):Is Severe Hypertension Just an Elevated Blood Pressure?

To determine whether clinical outcomes differed by occurrence of severe hypertension in the international CHIPS trial (Control of Hypertension in Pregnancy Study), adjusting for the interventions of textquotedblleftless tighttextquotedblright (target diastolic blood pressure [dBP] 100 mm Hg) versus textquotedbllefttighttextquotedblright control (target dBP 85 mm Hg). In this post-hoc analysis of CHIPS data from 987 women with nonsevere nonproteinuric preexisting or gestational hypertension, mixed effects logistic regression was used to compare the following outcomes according to occurrence of severe hypertension, adjusting for allocated group and the influence of baseline factors: CHIPS primary (perinatal loss or high-level neonatal care for gt;48 hours) and secondary outcomes (serious maternal complications), birth weight lt;10th percentile, preeclampsia, delivery at lt;34 or lt;37 weeks, platelets lt;100texttimes109/L, elevated liver enzymes with symptoms, maternal length of stay >=10 days, and maternal readmission before 6 weeks postpartum. Three hundred and thirty-four (34.1 women in CHIPS developed severe hypertension that was associated with all outcomes examined except for maternal readmission (P=0.20): CHIPS primary outcome, birth weight lt;10th percentile, preeclampsia, preterm delivery, elevated liver enzymes (all Plt;0.001), platelets lt;100texttimes109/L (P=0.006), and prolonged hospital stay (P=0.03). The association between severe hypertension and serious maternal complications was seen only in less tight control (P=0.02). Adjustment for preeclampsia (464, 47.3 did not negate the relationship between severe hypertension and the CHIPS primary outcome (Plt;0.001), birth weight lt;10th percentile (P=0.005), delivery at lt;37 (Plt;0.001) or lt;34 weeks (Plt;0.001), or elevated liver enzymes with symptoms (P=0.02). Severe hypertension is a risk marker for adverse maternal and perinatal outcomes, independent of BP control or preeclampsia co-occurrence.Clinical Trial RegistrationtextemdashURL: http://pre-empt.cfri.ca/. Unique identifier: ISRCTN 71416914. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01192412.Novelty and Significanc

Women's views and postpartum follow-up in the CHIPS Trial (Control of Hypertension in Pregnancy Study)

AbstractObjectiveTo compare women's views about blood pressure (BP) control in CHIPS (Control of Hypertension In Pregnancy Study) (NCT01192412).DesignQuantitative and qualitative analysis of questionnaire responses.SettingInternational randomised trial (94 sites, 15 countries).Population/sample911 (92.9%) women randomised to ‘tight’ (target diastolic blood pressure, 85mmHg) or ‘less tight’ (target diastolic blood pressure, 100mmHg) who completed questionnaires.MethodsA questionnaire was administered at ∼6–12 weeks postpartum regarding post-discharge morbidity and views about trial participation. Questionnaires were administered by the site co-ordinator, and contact was made by phone, home or clinic visit; rarely, data was collected from medical records. Quantitative analyses were Chi-square or Fisher's exact test for categorical variables, mixed effects multinomial logistic regression to adjust for confounders, and p<0.001 for statistical significance. NVivo software was used for thematic analysis of women's views.Main outcome measuresSatisfaction, measured as willingness to have the same treatment in another pregnancy or recommend that treatment to a friend.ResultsAmong the 533 women in ‘tight’ (N=265) vs. ‘less tight’ (N=268) control who provided comments for qualitative analysis, women in ‘tight’ (vs. ‘less tight’) control made fewer positive comments about the amount of medication taken (5 vs. 28 women, respectively) and intensity of BP monitoring (7 vs. 17, respectively). However, this did not translate into less willingness to either have the same treatment in another pregnancy (434, 95.8% vs. 423, 92.4%, respectively; p=0.14) or recommend that treatment to a friend (435, 96.0% and 428, 93.4%, respectively; p=0.17). Importantly, although satisfaction remained high among women with an adverse outcome, those in ‘tight’ control who suffered an adverse outcome (vs. those who did not) were not consistently less satisfied, whereas this was not the case among women in ‘less tight’ control among whom satisfaction was consistently lower for the CHIPS primary outcome (p<0.001), severe hypertension (p≤0.01), and pre-eclampsia (p<0.001).ConclusionsWomen in ‘tight’ (vs. ‘less tight’) control were equally satisfied with their care, and more so in the face of adverse perinatal or maternal outcomes

Control of Hypertension In Pregnancy Study randomised controlled trial-are the results dependent on the choice of labetalol or methyldopa?

Objective To determine whether the difference in outcomes between 'less tight' (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) in the CHIPS Trial (ISRCTN 71416914, http://pre-empt.cfri.ca/CHIPS) depended on the choice of labetalol or methyldopa, the two most commonly used antihypertensive agents in CHIPS. Design Secondary analysis of CHIPS Trial data. Setting International multicentre randomised controlled trial (94 sites, 15 countries). Population or sample A total of 987 women with non-severe non-proteinuric pregnancy hypertension. Methods Logistic regression was used for comparisons of 'less tight' versus 'tight' control among women treated with labetalol (but not methydopa) versus methyldopa (but not labetalol). Analyses were adjusted for the influence of baseline factors, including use of any antihypertensive therapy at randomisation. Main outcome measures Main CHIPS Trial outcomes: primary (perinatal loss or high-level neonatal care for > 48 hours), secondary (serious maternal complications), birthweight <10th centile, severe maternal hypertension, pre-eclampsia, and delivery at <34 or <37 weeks. Results Of 987 women in CHIPS, antihypertensive therapy was taken by 566 women at randomisation (labetalol 111 ['less tight'] versus 127 ['tight'] or methyldopa 126 ['less tight'] versus 117 ['tight']) and 815 women after randomisation (labetalol 186 ['less tight'] versus 247 ['tight'] and methyldopa by 98 ['less tight'] versus 126 ['tight']). Following adjustment, odds ratios for outcomes in 'less tight' versus 'tight' control were similar between antihypertensive groups according to 'at randomisation' and 'after randomisation' therapy. Conclusion Outcomes for 'less tight' versus 'tight' control were not dependent on use of methyldopa or labetalo

CHIPS-Child: Testing the developmental programming hypothesis in the offspring of the CHIPS trial

Objectives: As a follow-up to the CHIPS trial (Control of Hypertension In Pregnancy Study) of ‘less tight’ (versus ‘tight’) control of maternal blood pressure in pregnancy, CHIPS-Child investigated potential developmental programming of maternal blood pressure control in pregnancy, by examining measures of postnatal growth rate and hypothalamic-pituitary adrenal (HPA) axis activation. Methods: CHIPS follow-up was extended to 12 ± 2 months corrected post-gestational age for anthropometry (weight, length, head/waist circumference). For eligible children with consent for a study visit, we collected biological samples (hair/buccal samples) to evaluate HPA axis function (hair cortisol levels) and epigenetic change (DNA methylation analysis of buccal cells). The primary outcome was ‘change in z-score for weight’ between birth and 12 ± 2 mos. Secondary outcomes were hair cortisol and genome-wide DNA methylation status. Results: Of 683 eligible babies, 183 (26.8%) were lost to follow-up, 83 (12.2%) declined, 3 (0.4%) agreed only to ongoing contact, and 414 (60.6%) consented. 372/414 (89.9%) had weight measured at 12mos. In ‘less tight’ (vs. ‘tight’) control, the primary outcome was similar [−0.26 (−0.53, +0.01); p = 0.14, padjusted = 0.06]; median (95% confidence interval) hair cortisol (N = 35 samples) was lower [−496 (−892, −100) ng/g; p = 0.02], and buccal swab DNA methylation (N = 16 samples) was similar. No differences in growth rate could be demonstrated up to 5 years. Conclusions: Results demonstrate no compelling evidence for developmental programming of growth or the HPA axis. Clinicians should look to the clinical findings of CHIPS to guide practice. Researchers should seek to replicate these findings and extend outcomes to paediatric blood pressure and neurodevelopment.</p