Chronic hypertension in pregnancy stratified by first-trimester blood pressure control and adverse perinatal outcomes: A prospective observational study.

INTRODUCTION: The aim of this study was to assess perinatal outcomes in women with chronic hypertension (CH) stratified into four groups according to their blood pressure (BP) control in the first trimester of pregnancy. MATERIAL AND METHODS: This was a prospective cohort study between January 2011 and June 2017, based in a university hospital in London, UK. The population consisted of four groups: group 1 included women without history of CH, presenting in the first trimester with BP >140/90 mmHg (n = 100). Groups 2-4 had prepregnancy CH; group 2 had BP <140/90 mmHg without antihypertensives (n = 234), group 3 had BP <140/90 mmHg with antihypertensives (n = 272), and group 4 had BP ≥140/90 mmHg despite antihypertensives (n = 194). The main outcome measures were: fetal growth restriction, admission to neonatal (NNU) or neonatal intensive care unit (NICU) for ≥2 days, composite neonatal morbidity, and composite serious adverse neonatal outcome. Outcomes were collected from the hospital databases and for up to 6 weeks postnatally. Differences between groups were assessed using chi-squared test and multivariate logistic regression was used to assess the independent contribution of the four groups to the prediction of pertinent outcomes, after controlling for maternal characteristics. RESULTS: There was a higher incidence of fetal growth restriction in groups 3 (17.6%) and 4 (18.2%), compared with groups 1 (10.0%) and 2 (11.1%) (P = .04). There were more admissions to the NNU for ≥2 days in groups 3 (23.2%) and 4 (25.0%), compared with groups 1 (17.0%) and 2 (13.2%) (P = .008); and more admissions to NICU for ≥2 days in groups 3 (9.2%) and 4 (9.4%), compared with groups 1 (3.0%) and 2 (3.4%) (P = .01). Composite neonatal morbidity was higher in groups 3 (22.4%) and 4 (21.4%), compared with groups 1 (17.0%) and 2 (11.5%) (P = .009). Composite serious adverse postnatal outcome was higher in groups 3 (3.3%) and 4 (4.2%), compared with groups 1 (1.0%) and 2 (0.9%) but the difference did not reach statistical significance (P = .09). These results were also observed when values were adjusted for maternal characteristics. CONCLUSIONS: In CH adverse perinatal outcomes are worse in women who are known to have CH and need antihypertensives in the first trimester of pregnancy. Women with newly diagnosed CH in the first trimester have similar outcomes to those with known CH who have antihypertensive treatment discontinued.

First trimester inflammatory mediators in women with chronic hypertension.

INTRODUCTION: Chronic hypertension complicates 1%-2% of pregnancies and is one of the most significant risk factors for the development of preeclampsia. Inflammatory mediators, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule (VCAM) and endothelin have been implicated in the endothelial dysfunction that is pathognomonic of preeclampsia and may serve as useful first trimester biomarkers for the prediction of preeclampsia. The objectives of this study are: first, to investigate differences in serum levels of IL-6, TNF-α, VCAM and endothelin at 11+0 to 13+6 weeks' gestation in women with chronic hypertension who developed superimposed preeclampsia with those who did not and normotensive controls and, second, to evaluate the performance of these biomarkers in the prediction of preeclampsia. MATERIAL AND METHODS: The study population was comprised of 650 women with chronic hypertension, including 202 who developed superimposed preeclampsia and 448 who did not, and 142 normotensive controls matched to the chronic hypertension group for storage time and racial origin. Serum concentrations of IL-6, TNF-α, VCAM and endothelin were measured and the values were converted into multiples of the expected median using multivariate regression analysis in the control group. The multiples of the median values of the biomarkers between the two groups of women with chronic hypertension and the controls were compared, and the receiver operating characteristic curve (ROC) was used to assess the performance of these variables for the prediction of preeclampsia. RESULTS: In women with chronic hypertension, compared with the normotensive controls, there was a significantly higher first trimester median concentration of endothelin but not of VCAM, IL-6 or TNF-α. Within the cohort of women with chronic hypertension, those who developed superimposed preeclampsia, compared with those who did not, had higher first trimester serum concentration of VCAM but not of endothelin, IL-6 or TNF-α. However, serum VCAM provided a poor prediction of superimposed preeclampsia (area under the ROC curve 0.537, 95% CI 0.487-0.587). CONCLUSIONS: Women with chronic hypertension have increased serum endothelin in the first trimester of pregnancy and those who develop superimposed preeclampsia have higher levels of VCAM. None of the inflammatory mediators performed well in the first trimester in the prediction of preeclampsia.

First trimester serum angiogenic and anti-angiogenic factors in women with chronic hypertension for the prediction of preeclampsia.

BACKGROUND: An imbalance between angiogenic and antiangiogenic factors is thought to be a central pathogenetic mechanism in preeclampsia. In pregnancies that subsequently experience preeclampsia, the maternal serum concentration of the angiogenic placental growth factor is decreased from as early as the first trimester of pregnancy, and the concentration of the antiangiogenic soluble fms-like tyrosine kinase-1 is increased in the last few weeks before the clinical presentation of the disease. Chronic hypertension, which complicates 1-2% of pregnancies, is the highest risk factor for the development of preeclampsia among all other factors in maternal demographic characteristics and medical history. Two previous studies in women with chronic hypertension reported that first-trimester serum placental growth factor and soluble fms-like tyrosine kinase-1 levels were not significantly different between those who experienced superimposed preeclampsia and those who did not, whereas a third study reported that concentrations of placental growth factor were decreased. OBJECTIVE: The purpose of this study was to investigate whether, in women with chronic hypertension, serum concentrations of placental growth factor and soluble fms-like tyrosine kinase-1 and soluble fms-like tyrosine kinase-1/placental growth factor ratio at 11+0-13+6 weeks gestation are different between those women who experienced superimposed preeclampsia and those who did not and to compare these values with those in normotensive control subjects. STUDY DESIGN: The study population comprised 650 women with chronic hypertension, which included 202 women who experienced superimposed preeclampsia and 448 women who did not experience preeclampsia, and 142 normotensive control subjects. Maternal serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1 were measured by an automated biochemical analyzer and converted into multiples of the expected median with the use of multivariate regression analysis in the control group. Comparisons of placental growth factor and soluble fms-like tyrosine kinase-1 levels and soluble fms-like tyrosine kinase-1/placental growth factor ratio in multiples of the expected median values between the 2 groups of chronic hypertension and the control subjects were made with the analysis of variance or the Kruskal-Wallis test. RESULTS: In the group of women with chronic hypertension who experienced preeclampsia compared with those women who did not experience preeclampsia, there were significantly lower median concentrations of serum placental growth factor multiples of the expected median (0.904 [interquartile range, 0.771-1.052] vs 0.948 [interquartile range, 0.814-1.093]; P=.014) and soluble fms-like tyrosine kinase-1 multiples of the expected median (0.895 [interquartile range, 0.760-1.033] vs 0.938 [interquartile range, 0.807-1.095]; P=.013); they were both lower than in the normotensive control subjects (1.009 [interquartile range, 0.901-1.111] and 0.991 [interquartile range, 0.861-1.159], respectively; P<.01 for both). There were no significant differences among the 3 groups in soluble fms-like tyrosine kinase-1/placental growth factor ratios. In women with chronic hypertension, serum placental growth factor and soluble fms-like tyrosine kinase-1 levels provided poor prediction of superimposed preeclampsia (area under the curve, 0.567 [95% confidence interval, 0.537-0.615] and 0.546 [95% confidence interval, 0.507-0.585], respectively). CONCLUSION: Women with chronic hypertension, and particularly those who subsequently experienced preeclampsia, have reduced first-trimester concentrations of both placental growth factor and soluble fms-like tyrosine kinase-1.

Severe hypertension, preeclampsia and small for gestational age in women with chronic hypertension diagnosed before and during pregnancy.

OBJECTIVES: To compare rates of severe hypertension (SH), preeclampsia (PE) birth of small for gestational age (SGA) neonates between women with chronic hypertension (CH) diagnosed during the first trimester of pregnancy and those with pre-pregnancy CH. STUDY DESIGN: Prospective cohort study of women with CH and singleton pregnancies referred to an Antenatal Hypertension Clinic at 8-14 weeks' gestation. At presentation the patients were subdivided into four groups based on blood pressure (BP) control. Group 1 included women without a preceding history of CH presenting with BP of ≥140/90 mmHg (n = 86). Groups 2-4 had pre-pregnancy CH; in group 2 the BP was <140/90 mmHg without antihypertensive medication (n = 200), in group 3 the BP was <140/90 mmHg with antihypertensive medication (n = 231) and in group 4 the BP was ≥140/90 mmHg despite antihypertensive medication (n = 173). MAIN OUTCOME MEASURES: PE, SH (BP ≥ 160/110 mmHg), SGA (birthweight < 10th percentile). RESULTS: In group 1, the rate of SH (15.1%), was similar to that in group 2 (10.5%) and group 3 (23.8%) but significantly lower than in group 4 (52.6%). In group 1, the rate of PE (12.8%) and SGA <10th centile (18.6%) were similar to those in group 2 (16.5% and 21.0%) and significantly lower than in group 3 (26.0 and 30.7%) and group 4 (26.6% and 31.8). CONCLUSION: In women diagnosed with CH in the first trimester of pregnancy, the rates of SH, PE and SGA are similar to those with pre-pregnancy CH who present with BP below 140/90 without the need for antihypertensive medication.

Chronic hypertension: first-trimester blood pressure control and likelihood of severe hypertension, preeclampsia, and small for gestational age.

BACKGROUND: There is extensive evidence that prepregnancy chronic hypertension is associated with a high risk of development of severe hypertension and preeclampsia and birth of small-for-gestational-age neonates. However, previous studies have not reported whether antihypertensive use, blood pressure control, or normalization of blood pressure during early pregnancy influences the rates of these pregnancy complications. OBJECTIVE: The purpose of this study was to stratify women with prepregnancy chronic hypertension according to the use of antihypertensive medications and level of blood pressure control at the first hospital visit during the first trimester of pregnancy and to examine the rates of severe hypertension, preeclampsia, and birth of small-for-gestational-age neonates according to such stratification. STUDY DESIGN: We conducted a prospective study of 586 women with prepregnancy chronic hypertension, in the absence of renal or liver disease, that was booked at a dedicated clinic for the management of hypertension in pregnancy. The patients had singleton pregnancies and were subdivided according to findings in their first visit: group 1 (n=199), blood pressure <140/90 mm Hg without antihypertensive medication; group 2 (n=220), blood pressure <140/90 mm Hg with antihypertensive medication; and group 3 (n=167), systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg, despite antihypertensive medication. In the subsequent management of these pregnancies, our policy was to maintain the blood pressure at 130-140/80-90 mm Hg with the use of antihypertensive medication; antihypertensive drugs were stopped if the blood pressure was persistently <130/80 mm Hg. The outcome measures were severe hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥110 mm Hg), preterm and term preeclampsia (in addition to hypertension at least 1 of renal involvement, liver impairment, neurologic complications, or thrombocytopenia), and birth of small-for-gestational-age neonates (birthweight <5th percentile for gestational age). The incidence of these complications was compared in the 3 strata. RESULTS: The median gestational age at presentation was 10.0 weeks (interquartile range, 9.1-11.0 weeks). In groups 2 and 3, compared with group 1, there was a significantly higher body mass index, incidence of black racial origin, and history of preeclampsia in a previous pregnancy. There was a significant increase from group 1 to group 3 in the incidence of severe hypertension (10.6%, 22.2%, and 52.1%), preterm preeclampsia with onset at <37 weeks of gestation (7.0%, 15.9%, and 20.4%), and small for gestational age (13.1%, 17.7%, and 21.1%), but not term preeclampsia with onset at ≥37 weeks of gestation (9.5%, 9.1%, and 6.6%). CONCLUSIONS: In women with prepregnancy chronic hypertension, the rates of development of severe hypertension, preterm preeclampsia, and small for gestational age are related to the use of antihypertensive medications and the level of blood pressure control at the first hospital visit during the first trimester of pregnancy.

Pregnancy outcomes in women with previous gestational hypertension: A cohort study to guide counselling and management.

OBJECTIVES: In pregnant women with previous gestational hypertension: to compare the prevalence of preeclampsia as defined by the 2001 versus the 2014 International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria, to determine the rates of fetal growth restriction (FGR) as defined, not only by birthweight centile, but in combination with fetal ultrasound studies and, finally, to determine rates of other related outcomes such as gestational diabetes (GDM) and obstetric cholestasis (OC). STUDY DESIGN: This was a retrospective observational study based at the Antenatal Hypertension Clinic, Kings College Hospital, London. Routinely collected data of 773 women booked between 2011 and 2016 with a history of gestational hypertension was analysed. All women were normotensive at booking and those with chronic hypertension were excluded. MAIN OUTCOMES MEASURES: Hypertensive disorders of pregnancy (ISSHP-2014), FGR, GDM. RESULTS: Forty-nine percent developed one or more pregnancy complications, of which 72% were hypertensive disorders of pregnancy, 25.8% preeclampsia, 25% GDM and 19% FGR. Overall recurrence rate of preeclampsia was 12.5% (ISSHP-2014). Higher blood pressure and body mass index at booking were associated with higher risk of preeclampsia and GDM. Earlier gestation of previous hypertension was associated with higher risk of preeclampsia and FGR. The ISSHP-2014 compared to the 2001 guidelines classified 56% more women as having preeclampsia. CONCLUSION: Pregnant women with a history of gestational hypertension have a 49% chance of developing a complication related to a hypertensive disorder, GDM and OC. The rate of preeclampsia was more than doubled if the updated ISSHP-2014 definition was used.