Factors Associated with Refractory Severe Hypertension in Patients with Preeclampsia

• Materials and Methods
• Results
• Comment
• Principal Findings
• Results in the Context of What Is Known
• Clinical Implications
• Research Implications
• Strengths and Limitations
• Conclusion
• References

Abstract

Objective This study aimed to identify factors associated with refractory severe hypertension that does not resolve after an initial dose of antihypertensive medication in patients with preeclampsia.

Study Design This was a retrospective study of all pregnant and postpartum individuals with a diagnosis of preeclampsia, superimposed preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome, or eclampsia who delivered at 22 weeks or greater at a single academic institution from 2010 to 2020. Inclusion criteria were patients with preeclampsia who developed severe hypertension (systolic pressure ≥160 mm Hg or diastolic pressure ≥110 mm Hg) and received antihypertensive medications for acute severe hypertension. We defined refractory severe hypertension as a systolic blood pressure of ≥160 mm Hg or a diastolic blood pressure of ≥110 mm Hg that did not improve after receiving the initial treatment. To evaluate for factors associated with refractory severe hypertension, we developed multivariable modified Poisson regression using all variables with p-value <0.1 on bivariable analysis and calculated adjusted relative risks (aRRs) with 95% confidence intervals (95% CIs).

Results Of 850, 386 (45.4%) had refractory severe hypertension and 464 (54.6%) responded to the initial antihypertensive medications. Factors associated with refractory severe hypertension included higher body mass index (BMI), chronic hypertension, and higher systolic pressure. Every 5 kg/m² increase in BMI was associated with a 7% increased risk of refractory severe hypertension (aRR = 1.07; 95% CI: 1.02–1.12). Every 10 mm Hg increase in systolic blood pressure was associated with a 10% increased risk of refractory severe hypertension (aRR = 1.10; 95% CI: 1.04–1.17). Chronic hypertension was associated with a 25% increased risk of refractory severe hypertension (aRR = 1.25; 95% CI: 1.01–1.56) in the diastolic pressure model.

Conclusion Refractory severe hypertension was associated with elevated BMI, chronic hypertension, and higher systolic blood pressure.

Key Points

• Risk factors for refractory severe hypertension are not well-known.

• Almost half of the patients had refractory severe hypertension.

• Higher BMI, chronic hypertension, and higher systolic pressure were the risk factors.

• These patients would require closer follow-up and prompt response to vital signs.

Preeclampsia, one of the most common complications of pregnancy, complicates 5 to 7% of pregnancies and often presents as new-onset hypertension and proteinuria in the second or third trimester.[1] It is believed to be a result of abnormal placentation and can rapidly escalate to cause serious complications such as liver damage, kidney damage, myocardial infarction, and stroke.[1] [2] Preeclampsia is responsible for over 70,000 maternal deaths and 500,000 fetal deaths worldwide, each year.[3]

Management of preeclampsia includes treatment of severe hypertension, eclamptic seizure prevention by magnesium sulfate administration, and close maternal and fetal monitoring.[2] Adequate blood pressure control is critical for preeclampsia patients and hypertension refractory to treatment poses an increased risk for complications.[2] Preeclampsia and severe hypertension are the second most common cause of pregnancy-related deaths, following cardiovascular disease.[4] Intracerebral hemorrhage is the most common cause of preeclampsia-related deaths and accounts for 10 to 18% of overall maternal deaths.[5] [6] The California Pregnancy-Associated Mortality Review found that the leading factors of preeclampsia-related deaths were delays in seeking care (42%), underlying comorbidities (39%), and lack of knowledge regarding severe symptoms (39%); with up to 60% of preeclampsia-related deaths deemed preventable with prompt response to vital signs, education of patients and health care providers, and continuity of care.[4] Identifying individuals who are at risk for refractory severe hypertension would be helpful. We sought to identify risk factors that are most associated with severe hypertension that did not resolve after an initial antihypertensive medication. We also examined risk factors for refractory severe hypertension that did not resolve within 60 minutes of an initial dose of antihypertensive medication.

Materials and Methods

This was a retrospective study of all pregnant and postpartum individuals with a diagnosis of preeclampsia, superimposed preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome, or eclampsia who delivered at 22 weeks or greater at a single academic institution from 2010 to 2020. Analyses were limited to patients with preeclampsia who developed acute severe hypertension (systolic pressure ≥160 mm Hg or diastolic pressure ≥110 mm Hg) and received antihypertensive medications during the hospital stay. Our Institutional Review Board approved this analysis.

Preeclampsia was defined based on the American College of Obstetricians and Gynecologists (ACOG) definition.[7] Superimposed preeclampsia was defined as a diagnosis of preeclampsia in the setting of chronic hypertension. We used the International Classification of Diseases, Ninth Revision (ICD-9) (642.4, 642.5, 642.6, 642.7, and 646.9) and ICD-10 codes (O11, O14, and O15) to identify pregnant individuals eligible for this analysis. ICD-9 codes were used from 1999 to 2015, and ICD-10 codes from 2016 onwards. If a patient had more than one pregnancy in the dataset, we only included the first delivery in the analysis to avoid intrapersonal correlation. After identifying patients, a detailed chart review was conducted to confirm the diagnosis and abstract additional data. All blood pressure readings during the hospital admission were reviewed to identify the initial episode of severe hypertension.

In our practice, when severe hypertension is identified, the blood pressure is repeated after 15 minutes of the initial severe hypertension. If the subsequent blood pressure is severe, antihypertensive medications such as oral short-acting calcium channel blocker (nifedipine 10 mg), intravenous β-blocker (labetalol 20 mg), or intravenous hydralazine 5 mg, are administered.[7] If a patient is on long-acting antihypertensive medications, long-acting medications can be used at the attending physician's discretion.[7] If a patient does not respond to the initial antihypertensive medication, a standard escalation protocol is recommended.[8] Our primary exposure was refractory severe hypertension, which was defined as severe hypertension (systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥110 mm Hg) that has not improved to nonsevere levels after the initial treatment. Our secondary exposure was refractory severe hypertension that has not improved to nonsevere levels within 60 minutes after receiving the initial treatment. This primary exposure was chosen because this would not be affected by the treatment protocol (how frequently antihypertensive medications are administered). We chose the secondary exposure because a 60-minute cutoff is often used as a quality metric.[9]

We compared demographics and characteristics according to the exposures. Demographics included maternal age, body mass index (BMI; kg/m²), gestational age at the time of severe hypertension, race, parity, previous cesarean delivery, marital status, insurance status, smoking status, illicit drug use, and alcohol use. Characteristics included the presence of multiple gestation, pregestational diabetes, gestational diabetes, chronic hypertension, chronic kidney disease, cardiac disease, asthma, first severe blood pressure level (systolic and diastolic [mm Hg]), hypertension category (both systolic and diastolic severe, only systolic severe, and only diastolic severe), and the choice of initial medication. Chronic kidney disease was defined as the presence of kidney dysfunction based on the decreased glomerular filtration rate <60 mL/min/1.73 m² or kidney damage (urine albumin excretion of at least 30 mg/d).[10] Cardiac disease was defined as any congenital heart disease or acquired heart disease including heart failure, myocardial infarction, arrhythmia, or aortic dissection. Additionally, we examined the number of antihypertensive medications patients received (total and within 60 min from the initial dose) to assess whether those patients who had refractory severe hypertension after 60 minutes of the initial treatment were appropriately treated. This variable was not included in the final model as it was in the causative pathway. To evaluate for factors associated with the primary and secondary exposures, we developed modified Poisson regression using all variables with p-value <0.1 by bivariable analysis and calculated adjusted relative risks (aRRs) with 95% confidence intervals (95% CIs). Because systolic and diastolic blood pressure and hypertension categories were expected to be correlated with each other, we developed three different models including each variable. All variables had very little missing information ([Supplementary Table S1] [available in the online version]). Therefore, we did not perform multiple imputations. All statistical analyses were performed using Stata 18.0 (StataCorp, College Station, TX).

Results

The cohort diagram is presented in [Fig. 1]. Of 1,552 patients with preeclampsia, 850 had severe hypertension and received an antihypertensive medication. Of 850 total identified subjects, 386 (45.4%) had refractory severe hypertension after the initial antihypertensive medication and 464 (54.6%) responded to the initial antihypertensive medications. Demographics and characteristics are presented in [Table 1]. Patients who had refractory severe hypertension after the initial antihypertensive medication compared with those who did respond to the initial antihypertensive medications were more likely to have higher BMI, earlier gestational age, chronic hypertension, chronic kidney disease, higher systolic blood pressure, higher diastolic blood pressure, and both systolic and diastolic severe hypertension (all p < 0.05). These variables were included in the multivariable models.

aRRs for refractory severe hypertension after the initial antihypertensive medication are presented in [Table 2]. Model 1 included BMI, gestational age, chronic hypertension, chronic kidney disease, and systolic pressure. Every 5 kg/m² increase in BMI was associated with a 7% increased risk of refractory severe hypertension (aRR = 1.07; 95% CI: 1.02–1.12). Every 10 mm Hg increase in systolic blood pressure was associated with a 10% increased risk of refractory severe hypertension (aRR = 1.10; 95% CI: 1.04–1.17). Model 2 included BMI, gestational age, chronic hypertension, chronic kidney disease, and diastolic pressure. In addition to BMI, chronic hypertension was associated with an increased risk of refractory severe hypertension (aRR = 1.25; 95% CI: 1.02–1.56). Diastolic pressure was not significantly associated with refractory severe hypertension. Model 3 included BMI, gestational age, chronic hypertension, chronic kidney disease, and hypertension category. Only BMI and chronic hypertension were significantly associated with refractory severe hypertension in this model.

Of 850 total identified subjects, 255 (30.0%) had refractory severe hypertension after 60 minutes of the initial antihypertensive medication and 595 (70.0%) responded to the antihypertensive medications. Demographics and characteristics for refractory severe hypertension after 60 minutes of the initial antihypertensive medication are presented in [Table 3]. Patients who had refractory severe hypertension after 60 minutes of the initial antihypertensive medication compared with those who did respond to antihypertensive medications were more likely to have higher BMI, chronic hypertension, higher systolic blood pressure, and higher diastolic blood pressure (all p < 0.05). These variables and chronic kidney disease (p = 0.09) were included in the multivariable models. aRRs for refractory severe hypertension after 60 minutes of the initial antihypertensive medication are presented in [Table 4]. Model 1 included maternal age, BMI, chronic hypertension, chronic kidney disease, and systolic pressure. Every 5 kg/m² increase in BMI was associated with a 6% increased risk of refractory severe hypertension (aRR = 1.06; 95% CI: 1.01–1.11). Every 10 mm Hg increase in systolic blood pressure was associated with an 11% increased risk of refractory severe hypertension (aRR = 1.11; 95% CI: 1.04–1.17). Model 2 included maternal age, BMI, chronic hypertension, chronic kidney disease, and diastolic pressure. Every 10 mm Hg increase in diastolic blood pressure was associated with a 10% increased risk of refractory severe hypertension (aRR = 1.10; 95% CI: 1.02–1.18).

The number of antihypertensive medications is presented in [Supplementary Table S2] (available in the online version). Only a third of patients who did not respond to the initial antihypertensive medication received more than one dose of antihypertensive medication within 60 minutes of the initial dose. However, 90% of patients who had refractory severe hypertension eventually received more antihypertensive medications after 60 minutes.

Comment

Principal Findings

In our cohort of patients with preeclampsia and severe hypertension, we identified factors that were associated with refractory severe hypertension after the initial antihypertensive medication and after 60 minutes of antihypertensive medication. Factors associated with refractory severe hypertension after the initial antihypertensive medication included higher BMI, chronic hypertension, and higher systolic pressure. Factors associated with refractory severe hypertension after 60 minutes of the initial antihypertensive medication included higher BMI, higher systolic pressure, and higher diastolic pressure. More than 30% of patients who developed severe hypertension continued to have severe hypertension 60 minutes after the initial antihypertensive medication.

Results in the Context of What Is Known

Poorly controlled blood pressure in the setting of preeclampsia is associated with increased complications and poorer pregnancy outcomes.[4] Severe hypertension complicates 20 to 40% of women with chronic hypertension.[11] [12] Severe hypertension is associated with considerably higher risks of adverse maternal and newborn outcomes.[13] In a study of 24 antepartum or postpartum patients who had a stroke with a documented blood pressure immediately before the stroke, the majority of women (23/24) had a systolic blood pressure of ≥160 mm Hg.[14] However, only 3 patients out of 24 received antihypertensive medications during the 6 hours before the stroke.[14] Treatment of severe hypertension is necessary to mitigate these adverse outcomes. The results of our study provide insight into which patients are more likely to experience refractory severe hypertension. Knowing which factors are associated with an increased risk of refractory severe hypertension will help guide anticipatory clinical decision-making in preeclampsia patients to improve overall outcomes in these patients.

Clinical Implications

It is concerning that only half of patients responded to the initial antihypertensive medication and only two-thirds of patients with severe hypertension had a resolution of severe hypertension within 60 minutes of the initial antihypertensive medication. This finding is consistent with the randomized controlled trial that compared intravenous labetalol and hydralazine which showed that 55% of individuals required more than 60 mg of labetalol and most individuals who were randomized to hydralazine required 10 to 15 mg.[15] Those patients with risk factors for refractory severe hypertension may need closer monitoring and aggressive treatment options. By anticipating refractory severe hypertension, caregivers could prepare additional antihypertensive medications or more aggressive treatments such as calcium channel blockers or β-blocker infusion pumps if the antihypertensive medications do not resolve severe hypertension. It is noteworthy that two-thirds of patients who had refractory severe hypertension after 60 minutes of the initial antihypertensive medication only received one dose of antihypertensive medications within this time frame. Therefore, close monitoring of vital signs and prompt administration of antihypertensive medications could reduce the risk of refractory severe hypertension.

Research Implications

Our study cannot prove causality of the associated factors with refractory severe hypertension given that this is a retrospective study. There may be unknown factors that are associated with refractory severe hypertension in patients with preeclampsia. While we identified patients who were at risk for refractory severe hypertension, the management of high-risk patients is unclear. For example, these high-risk patients may need higher doses of antihypertensive medications. However, a higher dose of medication could result in hypotension, which could lead to uteroplacental insufficiency or nonreassuring fetal heart tracing.[16] [17] A randomized controlled trial that compares a higher dose of antihypertensive medication with a lower dose in patients at the highest risk of developing refractory severe hypertension would be useful.

Our primary outcome was the refractory severe hypertension instead of the Society of Maternal-Fetal Medicine (SMFM) quality metric, which is a timely antihypertensive treatment within 60 minutes of the onset of the first severe hypertension.[9] The quality metric was chosen by SMFM because some patients are refractory even after the appropriate treatment so the resolution of severe hypertension after the initial treatment or within 60 minutes would not be the ideal metric. In a retrospective cohort study of 211 patients from 2016 to 2018 who had severe hypertension, only 103 (49%) received timely antihypertensive treatment within 60 minutes.[18] Because the SMFM quality metric guideline was published in 2022 and the prior study used the definition of timely treatment as an administration of antihypertensive medication within 60 minutes of confirmed severe hypertension (second severe hypertension, not the first severe hypertension),[8] future studies that examine the rate of timely treatment and its outcomes using the new SMFM quality metric would be helpful.

Strengths and Limitations

One of the limitations of this retrospective analysis is that our data were derived from a single academic institution and therefore a larger multicenter study would be helpful to confirm the generalizability. Another limitation of our study is that it is a retrospective study, and we are unable to assess causal relationships. While we used multivariable regression models to control for confounders, there could be residual confounding. Finally, for the analysis of refractory hypertension that does not resolve within 60 minutes after the initial antihypertensive medication, only a third of patients who had refractory severe hypertension received a second dose of antihypertensive medication within 60 minutes. Therefore, refractory severe hypertension after 60 minutes of the initial antihypertensive medication could have been due to less aggressive treatment. This finding highlights the opportunity for a quality improvement project.

Our study has several strengths. Instead of extracting data using electronic medical records, we reviewed charts to obtain data. Therefore, we are confident about the quality of the data. The dataset had a very low rate of missing information. Further, due to the chart review, we were able to use strict definitions of preeclampsia and persistent severe hypertension, which abided by the ACOG and SMFM quality metric guidelines, respectively.[7] [8] We also exclusively analyzed the first pregnancy with preeclampsia of each participant to eliminate intrapersonal correlation. Finally, our data could be used as a reference for future studies that examine the optimal treatment for patients with severe hypertension.

Conclusion

Our study provides clarity as to which factors are most associated with refractory severe hypertension. This knowledge will help identify which patients would need more careful follow-up and prompt response to vital signs.

Conflict of Interest

None declared.

Acknowledgments

We thank Drs. Kazuma Onishi, Saritha Attanagoda, and Yara H. Diab, for helping with data collection.

Note

This paper was presented at the 44th Annual Meeting—the Pregnancy Meeting of the Society for Maternal-Fetal Medicine, Gaylord National Harbor in National Harbor, MD, from February 11 to 14, 2024.

• References

• 1 Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res 2019; 124 (07) 1094-1112
  CrossrefPubMedSearch in Google Scholar
• 2 Ford ND, Cox S, Ko JY. et al. Hypertensive disorders in pregnancy and mortality at delivery hospitalization - United States, 2017-2019. MMWR Morb Mortal Wkly Rep 2022; 71 (17) 585-591
  CrossrefPubMedSearch in Google Scholar
• 3 CDC. Preeclampsia, Genomics and Public Health | Blogs. Published October 25, 2022. Accessed March 15, 2024 at: https://blogs.cdc.gov/genomics/2022/10/25/preeclampsia/
  PubMed
• 4 Main EK, McCain CL, Morton CH, Holtby S, Lawton ES. Pregnancy-related mortality in California: causes, characteristics, and improvement opportunities. Obstet Gynecol 2015; 125 (04) 938-947
  CrossrefPubMedSearch in Google Scholar
• 5 Bateman BT, Schumacher HC, Bushnell CD. et al. Intracerebral hemorrhage in pregnancy: frequency, risk factors, and outcome. Neurology 2006; 67 (03) 424-429
  CrossrefPubMedSearch in Google Scholar
• 6 Foo L, Bewley S, Rudd A. Maternal death from stroke: a thirty year national retrospective review. Eur J Obstet Gynecol Reprod Biol 2013; 171 (02) 266-270
  CrossrefPubMedSearch in Google Scholar
• 7 American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 202: Gestational hypertension and preeclampsia. Obstet Gynecol 2019; 133 (01) 1
  PubMedSearch in Google Scholar
• 8 Committee on Obstetric Practice. Committee Opinion, Number 692: Emergent therapy for acute-onset, severe hypertension during pregnancy and the postpartum period. Obstet Gynecol 2017; 129 (04) e90-e95
  CrossrefPubMedSearch in Google Scholar
• 9 Combs CA, Allbert JR, Hameed AB, Main EK, Taylor I, Allen C. Society for Maternal-Fetal Medicine (SMFM), SMFM Patient Safety and Quality Committee. Electronic address: smfm@smfm.org. Society for Maternal-Fetal Medicine Special Statement: a quality metric for evaluating timely treatment of severe hypertension. Am J Obstet Gynecol 2022; 226 (02) B2-B9
  CrossrefPubMedSearch in Google Scholar
• 10 Stevens PE, Levin A. Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 2013; 158 (11) 825-830
  CrossrefPubMedSearch in Google Scholar
• 11 Magee LA, von Dadelszen P, Rey E. et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med 2015; 372 (05) 407-417
  CrossrefPubMedSearch in Google Scholar
• 12 Abalos E, Duley L, Steyn DW, Gialdini C. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev 2018; 10 (10) CD002252
  PubMedSearch in Google Scholar
• 13 Magee LA, von Dadelszen P, Singer J. et al; CHIPS Study Group*. The CHIPS Randomized Controlled Trial (Control of Hypertension in Pregnancy Study): is severe hypertension just an elevated blood pressure?. Hypertension 2016; 68 (05) 1153-1159
  CrossrefPubMedSearch in Google Scholar
• 14 Martin Jr JN, Thigpen BD, Moore RC, Rose CH, Cushman J, May W. Stroke and severe preeclampsia and eclampsia: a paradigm shift focusing on systolic blood pressure. Obstet Gynecol 2005; 105 (02) 246-254
  CrossrefPubMedSearch in Google Scholar
• 15 Mabie WC, Gonzalez AR, Sibai BM, Amon E. A comparative trial of labetalol and hydralazine in the acute management of severe hypertension complicating pregnancy. Obstet Gynecol 1987; 70 (3 Pt 1): 328-333
  PubMedSearch in Google Scholar
• 16 Impey L. Severe hypotension and fetal distress following sublingual administration of nifedipine to a patient with severe pregnancy induced hypertension at 33 weeks. Br J Obstet Gynaecol 1993; 100 (10) 959-961
  CrossrefPubMedSearch in Google Scholar
• 17 Puzey MS, Ackovic KL, Lindow SW, Gonin R. The effect of nifedipine on fetal umbilical artery Doppler waveforms in pregnancies complicated by hypertension. S Afr Med J 1991; 79 (04) 192-194
  PubMedSearch in Google Scholar
• 18 Vuncannon DM, Platner MH, Boulet SL. Timely treatment of severe hypertension and risk of severe maternal morbidity at an urban hospital. Am J Obstet Gynecol MFM 2023; 5 (02) 100809
  CrossrefPubMedSearch in Google Scholar

Address for correspondence

Publication History

Received: 19 April 2024

Accepted: 17 May 2024

Accepted Manuscript online:
20 May 2024

Article published online:
21 June 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

• References

• 1 Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res 2019; 124 (07) 1094-1112
  CrossrefPubMedSearch in Google Scholar
• 2 Ford ND, Cox S, Ko JY. et al. Hypertensive disorders in pregnancy and mortality at delivery hospitalization - United States, 2017-2019. MMWR Morb Mortal Wkly Rep 2022; 71 (17) 585-591
  CrossrefPubMedSearch in Google Scholar
• 3 CDC. Preeclampsia, Genomics and Public Health | Blogs. Published October 25, 2022. Accessed March 15, 2024 at: https://blogs.cdc.gov/genomics/2022/10/25/preeclampsia/
  PubMed
• 4 Main EK, McCain CL, Morton CH, Holtby S, Lawton ES. Pregnancy-related mortality in California: causes, characteristics, and improvement opportunities. Obstet Gynecol 2015; 125 (04) 938-947
  CrossrefPubMedSearch in Google Scholar
• 5 Bateman BT, Schumacher HC, Bushnell CD. et al. Intracerebral hemorrhage in pregnancy: frequency, risk factors, and outcome. Neurology 2006; 67 (03) 424-429
  CrossrefPubMedSearch in Google Scholar
• 6 Foo L, Bewley S, Rudd A. Maternal death from stroke: a thirty year national retrospective review. Eur J Obstet Gynecol Reprod Biol 2013; 171 (02) 266-270
  CrossrefPubMedSearch in Google Scholar
• 7 American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 202: Gestational hypertension and preeclampsia. Obstet Gynecol 2019; 133 (01) 1
  PubMedSearch in Google Scholar
• 8 Committee on Obstetric Practice. Committee Opinion, Number 692: Emergent therapy for acute-onset, severe hypertension during pregnancy and the postpartum period. Obstet Gynecol 2017; 129 (04) e90-e95
  CrossrefPubMedSearch in Google Scholar
• 9 Combs CA, Allbert JR, Hameed AB, Main EK, Taylor I, Allen C. Society for Maternal-Fetal Medicine (SMFM), SMFM Patient Safety and Quality Committee. Electronic address: smfm@smfm.org. Society for Maternal-Fetal Medicine Special Statement: a quality metric for evaluating timely treatment of severe hypertension. Am J Obstet Gynecol 2022; 226 (02) B2-B9
  CrossrefPubMedSearch in Google Scholar
• 10 Stevens PE, Levin A. Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 2013; 158 (11) 825-830
  CrossrefPubMedSearch in Google Scholar
• 11 Magee LA, von Dadelszen P, Rey E. et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med 2015; 372 (05) 407-417
  CrossrefPubMedSearch in Google Scholar
• 12 Abalos E, Duley L, Steyn DW, Gialdini C. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev 2018; 10 (10) CD002252
  PubMedSearch in Google Scholar
• 13 Magee LA, von Dadelszen P, Singer J. et al; CHIPS Study Group*. The CHIPS Randomized Controlled Trial (Control of Hypertension in Pregnancy Study): is severe hypertension just an elevated blood pressure?. Hypertension 2016; 68 (05) 1153-1159
  CrossrefPubMedSearch in Google Scholar
• 14 Martin Jr JN, Thigpen BD, Moore RC, Rose CH, Cushman J, May W. Stroke and severe preeclampsia and eclampsia: a paradigm shift focusing on systolic blood pressure. Obstet Gynecol 2005; 105 (02) 246-254
  CrossrefPubMedSearch in Google Scholar
• 15 Mabie WC, Gonzalez AR, Sibai BM, Amon E. A comparative trial of labetalol and hydralazine in the acute management of severe hypertension complicating pregnancy. Obstet Gynecol 1987; 70 (3 Pt 1): 328-333
  PubMedSearch in Google Scholar
• 16 Impey L. Severe hypotension and fetal distress following sublingual administration of nifedipine to a patient with severe pregnancy induced hypertension at 33 weeks. Br J Obstet Gynaecol 1993; 100 (10) 959-961
  CrossrefPubMedSearch in Google Scholar
• 17 Puzey MS, Ackovic KL, Lindow SW, Gonin R. The effect of nifedipine on fetal umbilical artery Doppler waveforms in pregnancies complicated by hypertension. S Afr Med J 1991; 79 (04) 192-194
  PubMedSearch in Google Scholar
• 18 Vuncannon DM, Platner MH, Boulet SL. Timely treatment of severe hypertension and risk of severe maternal morbidity at an urban hospital. Am J Obstet Gynecol MFM 2023; 5 (02) 100809
  CrossrefPubMedSearch in Google Scholar

• Supplementary Material