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

Abstract

IntroductionFor women with chronic or gestational hypertension in CHIPS (Control of Hypertension In Pregnancy Study, NCT01192412), we aimed to examine whether clinical predictors collected at randomization could predict adverse outcomes.Material and methodsThis was a planned, secondary analysis of data from the 987 women in the CHIPS Trial. Logistic regression was used to examine the impact of 19 candidate predictors on the probability of adverse perinatal (pregnancy loss or high level neonatal care for >48 h, or birthweight <10th percentile) or maternal outcomes (severe hypertension, preeclampsia, or delivery at <34 or <37 weeks). A model containing all candidate predictors was used to start the stepwise regression process based on goodness of fit as measured by the Akaike information criterion. For face validity, these variables were forced into the model: treatment group (“less tight” or “tight” control), antihypertensive type at randomization, and blood pressure within 1 week before randomization. Continuous variables were represented continuously or dichotomized based on the smaller p‐value in univariate analyses. An area‐under‐the‐receiver‐operating‐curve (AUC ROC) of ≥0.70 was taken to reflect a potentially useful model.ResultsPoint estimates for AUC ROC were <0.70 for all but severe hypertension (0.70, 95% CI 0.67–0.74) and delivery at <34 weeks (0.71, 95% CI 0.66–0.75). Therefore, no model warranted further assessment of performance.Conclusions CHIPS data suggest that when women with chronic hypertension develop an elevated blood pressure in pregnancy, or formerly normotensive women develop new gestational hypertension, maternal and current pregnancy clinical characteristics cannot predict adverse outcomes in the index pregnancy.

Gestational systolic blood pressure trajectories and risk of adverse maternal and perinatal outcomes in Chinese women

“…The current study also suggested that association magnitudes between SBP trajectories and the above-mentioned neonate outcomes depended mainly on the absolute SBP values in the third trimester. Consistently, studies found that BP elevation from the second trimester to the third trimester was associated with an increased risk of adverse birth outcomes [ 10 , 45 ]. What’s more, a Chinese study found a dose-response relationship between maternal BP and adverse birth outcomes, and BP in the third trimester showed the strongest associations [ 46 ].…”

The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy

“…Additionally, the administration of prophylactic calcium and or aspirin may have caused treatment paradox [84] that modified the effect of the risk factors on the development and outcomes of PE among the participants. The possible alteration of the circulating levels of angiogenic factors by aspirin reported in a previous study [85] is noted.…”

The CHIPS Randomized Controlled Trial (Control of Hypertension in Pregnancy Study)

“…In the CHIPS trial, women randomized to less tight control more frequently developed severe hypertension, and predictive modeling was unable to identify which women were destined to do so. 2 , 3 Both severe hypertension and preeclampsia, a recognized risk marker for adverse outcome, were common (33.9% and 47.3%, respectively) and often developed in the same woman (25.3%), but neither severe hypertension nor preeclampsia fully accounted for all women with one or more of the adverse outcomes considered. However, severe hypertension was associated with higher rates of each of the CHIPS primary perinatal outcome, birth weight <10th percentile, preeclampsia, delivery at <34 or 37 weeks, platelets <100×10 9 /L, elevated liver enzymes with symptoms, and maternal length of hospital stay ≥10 days.…”

“…In addition, predictive modeling did not demonstrate that women destined to develop subsequent severe hypertension could be identified by clinical characteristics at randomization, when a BP management strategy was instituted. 3 …”

“…The CHIPS trial has generated controversy over whether the increase in severe hypertension associated with less tight control merits a recommendation to use tight control because there is disagreement about whether the increased frequency of severe hypertension with less tight control: (1) is important to prevent because it would otherwise translate into an excess of adverse maternal outcomes for which CHIPS was underpowered to detect; (2) represents any risk to the fetus; or (3) can be identified easily and treated promptly in the course of antenatal care. 3 In this secondary analysis of CHIPS data, we sought to examine whether the occurrence of severe hypertension was associated with adverse perinatal and maternal outcomes, independent of allocated group and the occurrence of preeclampsia, one of the recognized pathways to adverse outcomes for hypertensive mothers and their babies.…”