Kilpatrick2016.pdf

Accepted Manuscript Severe Maternal Morbidity in a Large Cohort of Women with Acute Severe Intrapartum Hypertension Sarah J. Kilpatrick, MD, PhD, Ms. Anisha Abreo, MPH, Naomi Greene, PhD, Ms. Kathryn Melsop, MS, Ms. Nancy Peterson, MSN, RNC-OB, PNNP, IBCLC, Larry E. Shields, MD, Elliot K. Main, MD PII:

S0002-9378(16)00226-X

DOI:

10.1016/j.ajog.2016.01.176

Reference:

YMOB 10906

To appear in:

American Journal of Obstetrics and Gynecology

Received Date: 30 October 2015 Revised Date:

15 January 2016

Accepted Date: 22 January 2016

Please cite this article as: Kilpatrick SJ, Abreo A, Greene N, Melsop K, Peterson N, Shields LE, Main EK, Severe Maternal Morbidity in a Large Cohort of Women with Acute Severe Intrapartum Hypertension, American Journal of Obstetrics and Gynecology (2016), doi: 10.1016/j.ajog.2016.01.176. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT 1 Severe Maternal Morbidity in a Large Cohort of Women with Acute Severe Intrapartum

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Hypertension

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Ms. Anisha Abreo MPH2

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Naomi Greene PhD1

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Ms. Kathryn Melsop MS2

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Ms. Nancy Peterson MSN, RNC-OB, PNNP, IBCLC 2

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Larry E. Shields MD3

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Elliot K. Main MD2

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Sarah J. Kilpatrick MD, PhD1

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Cedars-Sinai Medical Center, Department of Obstetrics and Gynecology, Los Angeles, CA;

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California Maternal Quality Care Collaborative, Stanford University, Palo Alto, CA

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Patient Safety, Dignity Health, San Francisco, CA; Maternal Fetal Medicine, Marian Regional

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Medical Center, Santa Maria, CA

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The authors report no conflict of interest

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Corresponding Author:

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Sarah Kilpatrick MD, PhD

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Cedars-Sinai Medical Center, Department of Obstetrics and Gynecology

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8635 W. 3rd Street, Suite 160 West, Los Angeles, CA 90048

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Phone: 310-423-7433

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Email: [email protected]

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Word Count: Abstract: 489; Text 2623

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Table 4 should be included in the print issue

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Fax: 310-423-3470

ACCEPTED MANUSCRIPT 2 Condensation

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Women with acute severe intrapartum hypertension had a significant increased risk of severe

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maternal morbidity, 17% did not receive antihypertensive treatment, and lower delivery volume

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hospitals had higher severe maternal morbidity rates.

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Severe maternal morbidity and intrapartum severe hypertension

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ACCEPTED MANUSCRIPT 3 Abstract

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Background: Hypertensive diseases of pregnancy are associated with severe maternal morbidity and remain common causes of maternal death. Recently, national guidelines have become available to aid in recognition and management of hypertension in pregnancy to reduce morbidity and mortality. The increased morbidity related to hypertensive disorders of pregnancy is presumed to be associated with the development of severe hypertension. However, there are few data on specific treatment or severe maternal morbidity of women with acute severe intrapartum hypertension as opposed to severe preeclampsia.

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Objectives: The objectives were to characterize maternal morbidity associated with women with acute severe intrapartum hypertension and to determine if there was an association between various first line antihypertensive agents and post-treatment blood pressure.

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Study Design: This retrospective cohort study of women delivering between July 2012 and August 2014 at 15 hospitals participating in California Maternal Quality Care Collaborative compared women with severe intrapartum hypertension (systolic blood pressure > 160 mm Hg or diastolic blood pressure > 105 mm Hg) to women without severe hypertension. Hospital Patient Discharge Data and State of California Birth Certificate Data were used. Severe maternal morbidity using the Center for Disease Control and Prevention criteria based on international classification of diseases – 9 codes was compared between groups. The efficacy of different antihypertensive medications in meeting the one hour post-treatment goal was determined. Statistical methods included distribution appropriate univariate analyses and multivariate logistic regression.

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Results: There were 2252 women with acute severe intrapartum hypertension and 93,650 women without severe hypertension. Severe maternal morbidity was significantly more frequent in the women with severe hypertension (8.8%) compared to the control women (2.3%) (P<.0001). Severe maternal morbidity rates did not increase with increasing severity of blood pressures (P=0.90 for systolic and 0.42 for diastolic). There was no difference in severe maternal morbidity between women treated (8.6%) and the women not treated (9.5%) (P=0.56). Antihypertensive treatment rates were significantly higher in hospitals with a Level IV neonatal intensive care unit (85.8%) compared to a Level III neonatal intensive care unit (80.2%) (P<0.001), and in higher volume hospitals (84.5%) compared to lower volume hospitals (69.1%) (P<0.001). Severe maternal morbidity rates among severely hypertensive women were significantly higher in hospitals with Level III neonatal intensive care unit level compared to hospitals with a Level IV neonatal intensive care unit (10.6% vs. 5.7%, respectively) (P<0.001), and significantly higher in low delivery volume hospitals compared to high volume hospitals (15.5% vs. 7.6%, respectively) (P<0.001). Only 53% of women treated with oral labetalol as first line medication met the post-treatment goal of non-severe hypertension, significantly less than those treated with intravenous hydralazine, intravenous labetalol, or oral nifedipine (68, 71, 82%, respectively) (P=0.001). Severe intrapartum hypertension remained untreated in 17% of women.

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Conclusions: Women with acute severe intrapartum hypertension had a significantly higher risk for severe maternal morbidity compared to women without severe hypertension. Significantly lower antihypertensive treatment rates and higher severe maternal morbidity rates were seen in lower delivery volume hospitals.

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Key words: hypertension, severe maternal morbidity, severe preeclampsia

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INTRODUCTION It is well known that preeclampsia and other hypertensive diseases of pregnancy are associated

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with severe maternal morbidity including stroke, eclampsia, HELLP syndrome, renal failure and

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disseminated intravascular coagulation (DIC),1,2 and are a common cause of maternal death in

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the United States. 3,4 Further, more than half of maternal deaths due to hypertensive disease were

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deemed preventable.5,6 Because the increased morbidity related to hypertensive disorders of

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pregnancy is in part presumed to be associated with the development of severe hypertension,

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national and international guidelines, bundles and toolkits to aid in timely recognition and

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management of hypertension in pregnancy to reduce perinatal morbidity and mortality have been

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available for at least three years.1,7-13 Further, although there are multiple small randomized

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controlled trials comparing one antihypertensive agent to another to control acute severe

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antenatal hypertension, these studies generally focused on immediate treatment results and did

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not evaluate impact on severe maternal morbidity.14 Therefore, the aims of this study were to

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characterize current management patterns of a large cohort of women with acute severe

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intrapartum maternal hypertension, determine the specific severe maternal morbidity associated

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with intrapartum severe hypertension compared to women without severe hypertension, and to

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determine efficacy of different first line antihypertensive agents in meeting post-treatment blood

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pressure goals.

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MATERIALS AND METHODS

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We conducted a retrospective cohort study of all women delivering between July 2012 and

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August 2014 at 15 hospitals participating in both the Active Track of the California Maternal

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Quality Care Collaborative (CMQCC) and the CMQCC’s Preeclampsia Collaborative,

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comparing women with acute severe intrapartum hypertension to women without severe 1/15/16

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hypertension. CMQCC’s mission is to reduce maternal and perinatal morbidity and mortality, principally by gathering, reviewing, and organizing pregnancy-related data from a variety of

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sources to be used for quality improvement research and initiatives. These data functions occur

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within the California Maternal Data Center. Active Track hospitals provide automatic uploading

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of Patient Discharge Data monthly and also manually upload supplemental data from chart

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review. All records are linked to the Birth Certificate Data from the State of California. The

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purpose of CMQCC’s Preeclampsia Collaborative was to engage obstetric hospitals to improve

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timely diagnosis and treatment of women with preeclampsia by utilizing the CMQCC

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preeclampsia toolkit.8 Data submitted included blood pressures, treatment drug, time of

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treatment, blood pressure response to treatment, demographic data, and maternal morbidity. In

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addition, hospital delivery volume and neonatal intensive care unit (NICU) level of care were

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collected.

We compared women with severe hypertension, defined as systolic blood pressure (SBP)

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> 160 mm Hg or diastolic blood pressure (DBP) > 105 mm Hg that was confirmed within one

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hour, to women without severe hypertension. DBP > 105 mm Hg was used because this was the

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definition of severe diastolic hypertension used initially by CMQCC and supported by data in the

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literature.1,8 Women without severe hypertension, all remaining women who delivered at the

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same hospitals in the same time period, are hereafter called the control group. For the severely

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hypertensive women only data from the first episode of confirmed severe hypertension and

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treatment for that episode were submitted to the Preeclampsia Collaborative and used, such that

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each woman had only one hypertensive episode studied. Hypertensive episode data included

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antihypertensive drug, pretreatment blood pressure and post-treatment blood pressure within 1

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hour of treatment, reasons for no treatment if not treated, and type of hypertensive disease.

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ACCEPTED MANUSCRIPT 7 Types of hypertensive diseases were eclampsia, severe preeclampsia, superimposed

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preeclampsia, gestational hypertension, and 'other' was used when the patient did not meet the

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usual criteria for any of the prior four categories. Variables compared between groups included

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demographics (age, pre-pregnancy body mass index, race/ethnicity, insurance), pregnancy

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characteristics (plurality, delivery route, gestational age at delivery), hospital level factors and

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severe maternal morbidity. The hospital level factors we included were American Association of

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Pediatrics (AAP) NICU level15 as a proxy for maternal level of care; and annual birth volume.

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Severe maternal morbidity (SMM) was determined from the Center for Disease Control and Prevention (CDC) Callaghan criteria based on international classification of diseases – 9

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(ICD-9) codes.16-18 The CDC Callaghan criteria included the following ICD-9 diagnoses: DIC,

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acute renal failure, pulmonary edema, adult respiratory distress syndrome, transfusion, puerperal

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cerebrovascular event, and ventilation.16,18 For complete list of CDC ICD-9 codes for SMM see

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the CDC website.17 In addition, we collected abruption and postpartum hemorrhage based on

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ICD-9 discharge codes. It was not possible to determine whether the SMM occurred before or

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after treatment for severe hypertension.

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Within the group of women with acute severe hypertension we compared those treated

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with those not treated, in terms of demographics, pregnancy characteristics, medication used,

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hospital-level factors, and occurrence of severe maternal morbidity. In addition, the efficacy,

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defined as achieving blood pressure < 160/105, of different first line antihypertensive

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medications used for controlling severe blood pressure was compared in the treated group.

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Finally, we compared SMM rate and treatment rate between three tiers of severe blood pressure

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using chi-square and a trend test. The three tiers were determined from natural cut points in a

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histogram of blood pressure ranges. Statistical methods for all analyses included distribution

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ACCEPTED MANUSCRIPT 8 appropriate univariate analyses (chi-square, ANOVA, and t-tests). We constructed multivariate

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logistic regression with specific perinatal outcomes including the CDC Callaghan morbidity

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criteria as the dependent variables, and treated vs. not treated as the independent predictors of

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interest. Where appropriate, we constructed hierarchical models to account for between-hospital

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differences. We used SAS 9.3 (Cary, North Carolina) for all analyses and the significance

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(alpha) level was set at P<0.05. Finally, Stanford University provided a determination of Non-

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human subjects research.

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There were 2252 women with acute severe intrapartum hypertension and 93,650 women without

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severe hypertension who delivered at one of the 15 participating hospitals in our time frame.

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Demographics and pregnancy characteristics are presented in Table 1. Obesity, maternal age

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greater than 35, and multiple gestation were significantly more common in women with severe

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hypertension compared to controls (P<.0001). Of particular interest, 50.4% of the severely

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hypertensive women compared to 8.0% of the control women delivered prematurely with 14.3%

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vs. 1.6% delivering before 32 weeks gestation, respectively (P<.0001). The distribution of

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underlying hypertension disease type for all women with severe hypertension was the following:

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severe preeclampsia (65%), superimposed preeclampsia (25%), other (6%), gestational

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hypertension (3%), and eclampsia (1%).

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Severe maternal morbidity was significantly more frequent in the women with severe

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hypertension (8.8%) compared to the control women (2.3%) (P<.0001) (Table 2). Also seen in

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Table 2, all morbidities except stroke were significantly more frequent in the severely

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hypertensive women (P<0.0001). Of note, although stroke was rare in both groups of women,

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ACCEPTED MANUSCRIPT 9 there was a trend toward significance in the hypertensive women (P=0.07). The mean

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gestational age at delivery was significantly lower in the severely hypertensive women (35.6

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+3.5 weeks) compared to the control women (38.7 + 2.1 weeks) (P<0.0001). Because severe

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range blood pressures varied over wide ranges (160-260 mm Hg systolic, and 105-167 mm Hg

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diastolic), we created distribution-based categories of increasing blood pressure severity (mildly

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severe, moderately severe, severely severe) and examined whether SMM and treatment rates

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increased with increasing blood pressure severity. The histogram distribution of pretreatment

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severe blood pressures showed three natural cut points for systolic: 160-172 mm Hg; 173-192

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mm Hg; 193-260 mm Hg; and for diastolic:105-112 mm Hg; 113-122 mm Hg; 123-167 mm Hg

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(Table 3). SMM rates did not increase with increasing severity of blood pressures (P=0.90 for

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systolic and 0.42 for diastolic) (Table 3). In addition to a chi-square test, a trend test was

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performed to confirm whether there were truly no differences in SMM based on severity of

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blood pressure range. The trend p=0.98 for systolic BP and p=.18 for diastolic BP (data not

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shown). However, treatment rates increased significantly with increasing severity of blood

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pressures (P<0.001 for systolic and P<0.04 for diastolic) (Table 3).

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Of the 2252 severely hypertensive women, 448 (20%) received no antihypertensive

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treatment. Fifty-nine of these women were not treated because their blood pressure had returned

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to a non-severe range before a medication was given, leaving 389 or 17.3% of persistently

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hypertensive women who did not receive acute antihypertensive treatment. The other indications

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for not treating were magnesium started instead (54%), competing priorities (ultrasound, labs,

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magnesium) (4%), lack of knowledge about treatment parameters (3.6%), fear of hypotension

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(0.9%), RN reluctant to treat with intravenous (IV) medication (0.2%), and unknown (24%). All

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comparisons between treated and not treated women excluded the 59 women not treated because

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ACCEPTED MANUSCRIPT 10 their repeat blood pressure was no longer severe leaving 389 women in the not treated group.

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The mean qualifying blood pressure was significantly higher in the treated (176/102 mm Hg)

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compared to the women not treated (170/99 mm Hg) (P<0.0004). There was no difference in

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SMM between women treated (155/1804: 8.6%) and the women not treated (37/389: 9.5%)

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(P=0.56). Race, prepregnancy BMI, and maternal age were not significantly different between

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the treated and not treated hypertensive women. However, significantly more women who were

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treated delivered at less than 37 weeks gestation (52.3%) compared to women not treated

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(45.1%) (P=0.009).

Antihypertensive treatment rates and SMM rates differed significantly across categories

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of hospital-level factors (annual birth volume and AAP NICU level)15 (Table 4). Anti-

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hypertensive treatment rates were significantly higher in hospitals with a Level IV NICU

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(85.8%) compared to a Level III NICU (80.2%) (P<0.001), and in higher volume (>2500

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deliveries annually) hospitals (84.5%) compared to lower volume (<2500 deliveries annually)

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hospitals (69.1%) (P<0.001) (Table 4). Additionally, the SMM rates among severely

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hypertensive women were significantly higher in hospitals with Level III NICU level compared

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to hospitals with a Level IV NICU (10.6% vs. 5.7%, respectively) (P<0.001), and significantly

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higher in low delivery volume hospitals compared to high volume hospitals (15.5% vs. 7.6%,

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respectively) (P<0.001). Therefore we constructed a multilevel logistic model to assess the

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association of treatment on occurrence of SMM taking into account both pertinent patient-level

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(maternal age, race, pre-pregnancy BMI, plurality, delivery mode, and insurance) and the above

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mentioned hospital-level factors. Antihypertensive treatment remained a non-significant

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predictor of SMM even after these adjustments (P=0.78).

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As seen in Table 5, only 53% of women treated with oral labetalol met the post-treatment goal of non-severe hypertension (< 160/105), which was a significantly smaller proportion of

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women than those treated with IV hydralazine (68%), IV labetalol (71%), or oral nifedipine

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(82%) (P=0.001). The odds ratio was significantly higher for successful antihypertensive

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treatment for IV labetalol or IV hydralazine or oral nifedipine compared to oral labetalol

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(P<0.003) (Table 5). No significant difference was seen in the occurrence of severe maternal

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morbidity by antihypertensive drug used (P=0.43)

COMMENT

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The recent national focus on diagnosis and treatment of preeclampsia and severe hypertension

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with the intention of reducing maternal morbidity and mortality due to hypertensive disease is

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welcome particularly given the increasing prevalence of hypertensive disorders accompanying

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delivery admissions.7,8,19,20 However, there are few data specifically focused on women with

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intrapartum acute severe hypertension (as opposed to severe preeclampsia) on acute

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antihypertensive treatment and severe maternal morbidity. In this retrospective cohort study

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comparing 2252 women with acute severe intrapartum hypertension to over 93,000 women

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without severe hypertension, severe maternal morbidity was indeed significantly more common

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in the hypertensive women (8.8% vs. 2.3%). The national rate of SMM using the CDC ICD-9

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codes was 1.3% suggesting that this 8.8% rate is truly an elevated rate.16 A recurrent finding was

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the high preterm delivery rate in women with severe hypertension (50%) compared to women

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without severe hypertension (8%).21,22 Particularly of note was that 14% of the women with

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severe hypertension delivered at less than 32 weeks gestation compared to only 1.6% of the

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women without severe hypertension. It is interesting to speculate that the very low stroke rate in

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the hypertensive women (0.09%), may be related to the high premature delivery rate as a

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response to national guidelines that recommend delivery as early as 34 weeks for women with

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severe preeclampsia to reduce maternal morbidity of preeclampsia.7 Of note, 17% of women with persistent severe hypertension were not treated with

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antihypertensive medication and the most common reason (54%) for not treating these women

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was magnesium sulfate was started instead. Magnesium sulfate is not recommended as an

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antihypertensive treatment and these findings highlight an opportunity for improvement since all

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guidelines recommend antihypertensive treatment for severe hypertension and at least two

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directly state that magnesium sulfate is not recommended as an antihypertensive agent.13,19,23

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The SMM rate among women with a lesser degree of hypertension (160-172/105-112) was just

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as high as women with a more severe degree of hypertension (193-260/123-167), strongly

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suggesting that it is important to treat all women with severe BPs. The reduced efficacy of oral

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labetalol in meeting post-treatment BP goal (53%) compared to nifedipine (82%), IV labetalol

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(71%) or IV hydralazine (68%) is consistent with randomized controlled trials (RCT).14 In the

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only RCT that included oral labetalol, labetalol was effective in controlling BP 47% of the time

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which was not significantly different from methyldopa which had 56% efficacy.14,24 Further, the

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post-treatment response, of women treated with IV labetalol, IV hydralazine, or oral nifedipine,

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71%, 68% and 82%, respectively, is also consistent with multiple RCTs which reported 79 –

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84% rates of effective post-treatment responses to these first line medications.14 In our

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population nifedipine was the least used antihypertensive agent which is interesting given that

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data from randomized controlled trials of antihypertensive treatment for severe hypertension

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revealing high rates of post-treatment efficacy of nifedipine have been available since at least the

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1990’s.14

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Finally, it was concerning that the SMM rate was significantly higher in lower delivery volume and level III NICU hospitals compared to the higher delivery volume and level IV NICU

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hospitals. In parallel, the treatment rates were significantly less in lower delivery volume and

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level III NICU hospitals compared to higher delivery volume and level IV NICU hospitals.

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Although these data need further affirmation, they suggest that higher level of care and/or higher

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delivery volume hospitals may be more familiar or comfortable with the management of women

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with severe hypertension. Since NICU level is only a proxy for maternal level of care, these data

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also support recent recommendations to establish maternal levels of care and regionalization of

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care to promote inter-hospital relationships focused on education and quality.25

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The strengths of our study include that it reflects current practice in of a large cohort of pregnant women with acute severe hypertension in nonresearch settings, that these women were

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from a variety of urban and suburban hospitals in California (and Arizona) making the data

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broadly generalizable, and that severe maternal morbidity was measured using nationally

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accepted administrative criteria.16 However, one of the weaknesses of the study is its design

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precluded the ability to show any potential benefit of antihypertensive treatment on incidence of

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SMM because we were not able to determine when the morbidity occurred relative to the

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antihypertensive treatment. In addition, SMM diagnosis was based solely on ICD-9 codes

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without confirmatory chart review and it is known that positive and negative predictive values of

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ICD-9 codes are problematic.26 Finally, these data were based on the first episode of severe

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hypertension and so we were unable to control for multiple episodes of severe hypertension.

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Future prospective studies are needed to better characterize the impact of early diagnosis and

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acute treatment of pregnant women with severe hypertension.

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ACCEPTED MANUSCRIPT 14 In conclusion, compared to pregnant women without severe hypertension, pregnant

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women with acute severe hypertension have a significantly higher risk for severe maternal

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morbidity. Significantly lower antihypertensive treatment rates and higher SMM rates were seen

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in lower delivery volume hospitals compared to higher delivery volume hospitals. Despite

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strong recommendations for antihypertensive treatment of acute severe intrapartum hypertension,

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17% women remained untreated. Finally, similar to existing randomized trial data, rates of

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adequate post-treatment BP control after treating acute severe hypertension were highest with

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nifedipine, IV labetalol and IV hydralazine.

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Gynecol 2015;125:521-5.

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353

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morbidity in the United States. Obstet Gynecol 2009;113:1299-306.

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367 368 369

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361

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358

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371 372

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ACCEPTED MANUSCRIPT 18 Table 1. Demographics in Women with and without Severe Hypertension Severe HTN

No Severe HTN

(n = 2252)

(n = 93,650)

%

N

White, non-Latina

643

33.7

28,525

Black, non-Latina

11

0.6

327

Asian/Pacific Islander

7

0.4

Latina

1119

Prepregnancy Body Mass Indexb Underweight (<18.5)

0.3

58.7

52,110

60.7

127

6.7

4,721

5.5

28

1.7

3,035

3.9

531

31.3

38,407

49.2

TE D

Normal (18.5-25)

0.4

216

M AN U

Other/Refused/Unknown

33.2

SC

Racea

%

RI PT

N

479

28.3

19,858

25.4

Obese (> 30)

656

38.7

16,816

21.6

Under 20

118

6.2

4,457

5.2

20-29

700

36.7

37,737

43.9

30-34

557

29.2

25,686

29.9

35-39

397

20.8

14,334

16.7

≥ 40

135

7.1

3,723

4.3

Singletons

1778

93.2

84,196

98.0

EP

AC C

0.07

<.001

Overweight (25.1-30)

Maternal Age a

P value

<.001

Pluralitya

1/15/16

<.001

ACCEPTED MANUSCRIPT

Twins

124

6.5

1,690

2.0

Triplets or higher

5

0.3

52

0.1

Vaginal

782

41.0

59,810

70

Cesarean

1,125

58.9

26,128

Very Preterm (<32 wks)

272

14.3

1,340

Preterm (32-36 wks)

689

36.1

Term (> 37 wks)

946

SC

19

RI PT

Method of Deliverya

<.001

Gestational Age at Delivery

30

1.6 6.4

49.6

79,068

92.1

934

48.9

37,666

43.9

921

48.3

45,814

53.3

24

1.3

906

1.1

28

1.5

1,495

1.7

840

37.3

29,149

31.1

1412

62.7

64,501

68.9

Low (1100-2700)

425

18.9

25,886

27.6

Medium (2701-5800)

1452

64.5

50,545

54.0

High (5801-7000)

375

16.7

17,219

18.4

Insurance a Medicaid Private

Other AAP NICU Levelc

EP

Level IV

TE D

None/Uninsured

M AN U

5740

Level III

<.001

<.001

<.001

AC C

Annual Birth Volume

<0.001

Abbreviations: AAP NICU: American Association of Pediatrics Neonatal Intensive Care Unit; HTN: hypertension a Missing in 8% b Missing in 17% c American Association of Pediatrics. Levels of Neonatal Care. Pediatrics 2012; 130; 587 1/15/16

ACCEPTED MANUSCRIPT 20

Table 2. Severe Maternal Morbidity in Women with and without Severe Hypertension No Severe HTN

(n = 2252)

(n = 93,650) N

%

2178

2.3

< 0.001

SC

N

%

197

8.8

Severe Maternal Morbidities Total SMM (from Callaghan)

9

0.4

15

0.02

< 0.001

Acute Respiratory Distress Syndrome

19

0.84

51

0.05

< 0.001

Stroke

2

0.09

17

0.02

0.07

Transfusion

116

5.2

1096

1.2

< 0.001

Ventilation

14

0.6

47

0.05

< 0.001

Postpartum Hemorrhagea

228

10.1

4268

4.6

< 0.001

Placental Abruptiona

66

2.9

1015

1.1

< 0.001

M AN U

Pulmonary Edema

P Value

RI PT

Severe HTN

EP

Mean Length of Stay (SD)

TE D

Non-Callaghan Morbidities

Mean Gestational Age at Deliveryb (SD)

5.32 (4.45)

2.76 (2.45)

< 0.001

35.6 (3.5)

38.7 (2.1)

< 0.001

AC C

Abbreviations: HTN: hypertension; SD: standard deviation; SMM: severe maternal morbidity a Placental Abruption and Postpartum hemorrhage calculated independently of Callaghan's metric b Missing in 8%

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ACCEPTED MANUSCRIPT 21 Table 3. Antihypertensive Treatment and Severe Maternal Morbidity Rates by Increasing Blood Pressure Severity in Severely Hypertensive Women Categories of Severe Systolic Blood Pressure

Severe Maternal Morbidity

SMM

Severely

Mildly

Severe

Severe

Severe

(160-172)a

(173-192)a

(193-260)a

(105-112)a

N = 1000

N = 865

N = 202

N = 564

N (%)

N (%)

N (%)

790 (79.0)

741 (85.7)

184 (91.1)

N = 1037

N = 881

N = 204

N (%)

N (%)

N (%)

91 (8.8)

74 (8.4)

19 (9.3)

P

<0.001

Severe

Moderately

0.90

Severely

RI PT

Moderately

Severe

Severe

(113-122)a

(123-167)a

N = 246

N = 83

SC

Treated

Mildly

N (%)

N (%)

N (%)

464 (82.3)

220 (89.1)

72 (86.8)

N = 577

N = 250

N = 83

N (%)

N (%)

N (%)

47 (8.2)

25 (10.0)

10 (12.1)

M AN U

Treatment Statusb

Categories of Severe Diastolic Blood Pressure

P Value

0.04

0.42

AC C

EP

TE D

Abbreviation: SMM: severe maternal morbidity a All Blood Pressures are reported in mmHg. Blood pressure category cut-points were based on examination of the systolic and diastolic blood pressures by histogram. b Excludes 59 women whose blood pressure stabilized before treatment

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ACCEPTED MANUSCRIPT 22 Table 4. Antihypertensive Treatment Rates and Severe Maternal Morbidity by Hospital Characteristics in Severely Hypertensive Women AAP NICU Level

Annual Birth Volume

N = 821

N (%)

N (%)

Treatment Rate 1100 (80.2%) Severe Maternal Morbidity

SMM Rate

704 (85.8%)

N = 1412

N = 840

N (%)

N (%)

149 (10.6%)

48 (5.7%)

<0.001

<2500

<0.001

≥2500

N = 320

N = 1873

N (%)

N (%)

SC

N = 1372

P

221 (69.1%)

1583 (84.5%)

N = 330

N = 1922

M AN U

Treatment Status b

Level IVa

RI PT

P Level IIIa

N (%)

N (%)

51 (15.5%)

146 (7.6%)

Value

<0.001

<0.001

AC C

EP

TE D

Abbreviations: AAP NICU: American Academy of Pediatrics Neonatal Intensive Care Unit; SMM: Severe Maternal Morbidity a American Association of Pediatrics. Levels of Neonatal Care. Pediatrics 2012; 130; 587 b Excludes 59 women who were not treated because their blood pressure stabilized before treatment

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ACCEPTED MANUSCRIPT 23 Table 5. Treatment of Severe Hypertension by Drug Used Among 1804 Severely Hypertensive Women Met Pretreatment

Pretreatment

Column

Met Treatment Treatment

N

SBP

DBP

P

%

Goal

P

Goal Mean (SD)

OR (95%CL)

RI PT

Mean (SD)

N

Row %

Medication 611

33.9

177 (15)

102 (12)

418

68.4

IV Labetalol

1057

58.6

175 (14)

102 (12)

748

70.8

SC

IV Hydralazine

1.92 (1.24,2.95)

0.003

2.14 (1.41,3.25)

<0.001

3.92 (1.58,9.74)

0.003

1.00 (reference)

--

0.001

38

2.1

174 (14)

PO Labetolol

98

5.4

175 (15)

100 (12)

31

81.6

M AN U

PO Nifedipine

102 (10)

52

53.1

AC C

EP

TE D

Abbreviations: DBP: diastolic blood pressure; IV: intravenous; 95%CL: 95% confidence limits; OR: odds ratio; P: P-value; PO: Per Oral; SD: standard deviation

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