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Original Research

Perinatal Outcomes in Women With a History


of Chronic Hypertension but Normal Blood
Pressures Before 20 Weeks of Gestation
Mallory Youngstrom, MD, Alan Tita, MD, PhD, Janatha Grant, MSN, FNP-BC, Jeff M. Szychowski, PhD,
and Lorie M. Harper, MD, MSCI
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OBJECTIVE: To compare the perinatal outcomes of preterm birth before 37 and 34 weeks of gestation, small
normotensive women with those of women with a history for gestational age, and preeclampsia.
of chronic hypertension with normal blood pressures RESULTS: Of 830 women with chronic hypertension and
before 20 weeks of gestation, stratifying the latter by blood pressures less than 140/90 mm Hg before 20
whether they were receiving antihypertensive medica- weeks of gestation, 212 (26%) were not taking antihy-
tion. pertensive medication and 618 (74%) were. These groups
METHODS: We conducted a retrospective cohort study were compared with 476 women without chronic hyper-
of all singletons with a history of chronic hypertension tension. Women with hypertension were more likely to
from 2000 to 2014. Exclusions were blood pressure be older and have baseline renal disease and diabetes
greater than 140/90 mm Hg before 20 weeks of gestation, compared with women in the no hypertension group. The
fetal anomalies, major medical problems other than perinatal composite was more common in both hyperten-
hypertension, and diabetes. For the same time period, sive groups: no antihypertensive medication (9.9%) and
a randomly selected group without a diagnosis of chronic antihypertensive medication (14.6%) compared with
hypertension was chosen using the same exclusion women in the control group (2.9%) (adjusted odds ratio
criteria. Outcomes were compared among women with- [OR] 2.9, 95% CI 1.21–6.85 no antihypertensive medica-
out chronic hypertension, women with chronic hyper- tions compared with no chronic hypertension; adjusted
tension on no antihypertensive medication but with
OR 5.0, 95% CI 2.38–10.54 antihypertensive medications
blood pressures less than 140/90 mm Hg before 20
vs no chronic hypertension). The risk of early preterm
weeks of gestation, and women with chronic hyperten-
birth, small for gestational age, and preeclampsia was not
sion on antihypertensive medication with blood pres-
significantly increased in women with chronic hyperten-
sures less than 140/90 mm Hg before 20 weeks of
sion and no antihypertensive medications compared with
gestation. The primary outcome was a perinatal com-
women without chronic hypertension.
posite of stillbirth, neonatal death, respiratory support at
birth, arterial cord pH less than 7, 5-minute Apgar score 3 CONCLUSION: Despite normal baseline blood pres-
or less, and seizures. Secondary outcomes assessed were sures without medications before 20 weeks of gestation,
women with chronic hypertension are at an increased
risk of adverse perinatal outcomes compared with
women without.
From the Department of Gynecology and Obstetrics, Emory University, Atlanta,
Georgia; and the Department of Obstetrics and Gynecology, the University of (Obstet Gynecol 2018;131:827–34)
Alabama at Birmingham, Birmingham, Alabama. DOI: 10.1097/AOG.0000000000002574
Each author has indicated that he or she has met the journal’s requirements for
authorship.
Corresponding author: Lorie M. Harper, MD, MSCI, Department of Obstetrics
and Gynecology, the University of Alabama at Birmingham, 1700 6th Avenue
C hronic hypertension in pregnancy is associated
with an increased risk for preeclampsia, eclamp-
sia, preterm delivery, and perinatal mortality.1–3
South, Suite 10270, Birmingham, AL 35233; email: lmharper@uabmc.edu.
As a result of the normal physiology of preg-
Financial Disclosure
The authors did not report any potential conflicts of interest. nancy, including decreased vascular resistance, sys-
© 2018 by American College of Obstetricians and Gynecologists. Published by
tolic and diastolic blood pressures (BPs) fall in early
Wolters Kluwer Health, Inc. All rights reserved. gestation and continue to be 5–10 mm Hg below
ISSN: 0029-7844/18 baseline for most of the second trimester.4

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Consequently, many women with chronic hyperten- generator. Other than chronic hypertension, the same
sion will have normal BPs (less than 140/90 mm Hg) inclusion and exclusion criteria were used to select the
during pregnancy without medications. nonhypertensive group of women. Trained chart ab-
Little is known about this particular subgroup of stractors reviewed all charts with a standardized chart
pregnancies complicated by chronic hypertension; the abstraction form. Data were collected on demo-
majority of prior studies of chronic hypertension in graphic information, obstetric history, laboratory
pregnancy use only diagnostic codes or medication information, BP and urinalysis at each prenatal visit,
lists to assess the risks associated with chronic labor course, delivery information, and neonatal out-
hypertension. Whether women with a history of comes until discharge.
chronic hypertension but who remain normotensive Women were excluded from this analysis if
without medication during pregnancy are at increased BPs before 20 weeks of gestation were greater than
risk for stillbirth, fetal growth restriction, or other 140/90 mm Hg or if they reported major medical
adverse perinatal outcomes during pregnancy is not problems other than hypertension, diabetes, or base-
clear. line renal disease. Women were also excluded if fetal
The objective of this study is to assess perinatal anomalies were identified before neonatal discharge
outcomes in women to compare the perinatal out- from the hospital.
comes of normotensive women and women with All women with chronic hypertension were
a history of chronic hypertension with normal BPs treated per institutional protocol under the supervi-
before 20 weeks of gestation, stratifying the latter by sion of maternal–fetal medicine specialists, with target
whether they were receiving antihypertensive BPs less than 150/90 mm Hg. Serial fetal growth was
medication. assessed by ultrasonography after 28 weeks of gesta-
tion, and at least weekly antenatal testing was per-
MATERIALS AND METHODS formed with either contraction stress tests or
This study was a retrospective cohort study of all biophysical profiles starting at 32–34 weeks of
patients with chronic hypertension at the University gestation.
of Alabama at Birmingham who presented before 20 Outcomes were compared among the three
weeks of gestation for prenatal care from January 1, exposure groups. The primary outcome was a perina-
2000, to June 1, 2014. Institutional board review was tal composite of stillbirth, neonatal death, respiratory
obtained. support at birth, arterial cord pH less than 7, 5-minute
Three exposure groups were identified: 1) women Apgar score 3 or less, and seizures. Stillbirth and
without a diagnosis of chronic hypertension (and who neonatal death were additionally assessed as second-
had normal BPs before 20 weeks of gestation), 2) ary outcomes. Respiratory support was defined as
women with a history of chronic hypertension but not receiving continuous positive airway pressure or
taking antihypertensive medications who had normal mechanical ventilation for any amount of time. These
BPs before 20 weeks of gestation, and 3) women with outcomes were chosen because they are significantly
a history of chronic hypertension who were taking associated with death or long-term neurologic mor-
antihypertensive medications and had normal BPs bidity.5–9 Additional secondary outcomes were small
before 20 weeks of gestation. for gestational age (SGA; defined as birth weight less
Women with singleton gestations complicated by than the 10th percentile)10 and preterm birth at less
chronic hypertension were identified through the than 37 weeks of gestation and preterm birth at
perinatal database at the University of Alabama at less than 34 weeks of gestation. The primary maternal
Birmingham using a diagnosis of chronic hyperten- outcome was preeclampsia; secondary maternal out-
sion. The diagnosis of chronic hypertension was comes were severe preeclampsia and early-onset
confirmed by chart review based either on maternal severe preeclampsia. Preeclampsia was defined as
history (maternal report of current diagnosis of BPs 140/90 mm Hg or greater with either proteinuria
chronic hypertension) or the use of antihypertensive (protein excretion 300 mg or greater in 24 hours or
medication before pregnancy. Women who reported protein-to-creatinine ratio 0.3 or greater), thrombocy-
a history of “prehypertension” or who reported reso- topenia (less than 100,000/mL), transaminases (aspar-
lution of chronic hypertension after lifestyle modifica- tate aminotransferase greater than twice the upper
tion or weight loss were excluded. For the same time limit of normal), or elevated creatinine (1.2 mg/dL
period (2000–2014), a randomly selected group of or greater). Severe preeclampsia was defined as pre-
women without a diagnosis of hypertension (n5476) eclampsia plus a severe feature (BP 160/100 mm Hg
were chosen for comparison using a random number or greater or a serum laboratory abnormality);

828 Youngstrom et al Women With Chronic Hypertension but Normal Blood Pressures OBSTETRICS & GYNECOLOGY

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Fig. 1. Patient derivation.
Youngstrom. Women With Chronic
Hypertension but Normal Blood Pres-
sures. Obstet Gynecol 2018.

neurologic symptoms such as headache were not identified 625 charts to obtain 435 eligible normoten-
abstracted as a result of variability in recording and sive women as controls.
so not included in the definition. Early-onset severe Descriptive statistics were compared between the
preeclampsia was defined as severe preeclampsia exposure groups using analysis of variance, x2 test of
diagnosed before 34 weeks of gestation. trend, or Fisher exact, as appropriate. Because we ex-
Because hypertension in pregnancy is relatively pected that women without a diagnosis of chronic
rare, we collected data on all women with a diagnosis hypertension would have the lowest incidence of
of chronic hypertension from January 1, 2000, to June adverse outcomes and that women receiving antihy-
1, 2014. To determine the number of nonhypertensive pertensive medications would have the highest inci-
women required, we estimated that approximately dence of adverse outcomes, we used a x2 test for
800 women would be included in the study, the trend. Potentially confounding variables of the
primary perinatal composite outcome would occur in exposure–outcome association were identified in the
10% of hypertensive women,11,12 and that groups stratified analyses. Multivariable logistic regression
would be evenly distributed between receiving and models for the primary outcome were then developed
not receiving antihypertensive medications. To detect to estimate the effect of the exposure group. Co-
a 50% reduction in the risk of the primary perinatal variates for initial inclusion in multivariable statistical
composite outcome in women without hypertension models were selected using the results of the uni-
(or an incidence of 5%), with an a of 0.05 and a b of variable and stratified analyses as well as historic
0.2, 435 women without a diagnosis of chronic hyper- confounding variables (eg, history of preterm delivery
tension were required. Because we anticipated that the for preterm delivery, history of preeclampsia for
primary perinatal composite would be the least fre- preeclampsia), and factors were removed in a back-
quent outcome, we anticipated at least 80% power to ward stepwise fashion based on significant changes
detect a difference in our secondary outcomes of pre- (10%) in the exposure adjusted odds ratio or signifi-
term birth, preeclampsia, and SGA. We randomly cant differences between hierarchical models using
selected a group of women from the same time period the likelihood ratio test. Statistical analysis was per-
formed using STATA 13 Special Edition.
using the same exclusion criteria as for women with
chronic hypertension. To do this, we identified
women with singleton gestations from the same time RESULTS
period and no known diagnosis of chronic hyperten- Of 1,478 women with chronic hypertension over the
sion and assigned them a number using a random study period, 830 were included in the analysis
number generator. We then reviewed charts in order (Fig. 1). Of these, 212 (26%) had BPs less than 140/
of the random number generator. Because we antici- 90 mm Hg and did not receive antihypertensive med-
pated that 25–30% of women would be ineligible, we ication and 618 (74%) had BPs less than 140/90 mm

VOL. 131, NO. 5, MAY 2018 Youngstrom et al Women With Chronic Hypertension but Normal Blood Pressures 829

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Table 1. Maternal Demographics

No Chronic Chronic Hypertension, Less Than Chronic Hypertension, Less Than


Hypertension 140/90 mm Hg, No Antihypertensive 140/90 mm Hg, Antihypertensive
Demographic (n5476) Medication (n5212) Medications (n5618) P

Age (y) 24.865.9 28.965.8 30.565.9 ,.01


Race
Black 293 (61.7) 147 (69.3) 442 (71.5) ,.01
White 83 (17.5) 57 (26.9) 147 (23.8)
Hispanic 84 (17.7) 6 (2.8) 17 (2.8)
Other 15 (3.1) 2 (1) 12 (1.9)
Nulliparous 191 (40.1) 70 (33.0) 168 (27.2) ,.01
BMI (kg/m2) 28.567.5 39.0610.3 38.8611.0 ,.01
Tobacco use 72 (15.1) 47 (22.2) 118 (19.3) .06
Government 329 (69.1) 156 (73.6) 431 (69.7) ,.01
insurance
Pregnancy-induced 14 (2.9) 60 (28.36) 208 (33.7) ,.01
hypertension in
a prior
pregnancy
Antihypertensive 0 73 (34.4) 383 (62.4) ,.01
medications
before
pregnancy
Single agent before 0 0 509 (82.4) ,.01
20 wk of
gestation
More than 1 agent 0 0 109 (17.6) ,.01
before 20 wk
of gestation
Aspirin started during 2 (0.4) 10 (4.7) 59 (9.6) ,.01
pregnancy
Baseline renal disease 1 (0.2) 13 (6.1) 71 (11.5) ,.01
Diabetes
Gestational 13 (2.7) 25 (12.0) 79 (13.0) ,.01
Pregestational 12 (2.5) 61 (29.2) 138 (22.6)
BMI, body mass index.
Data are mean6SD or n (%) unless otherwise specified.

Hg but were receiving antihypertensive medication The primary composite adverse perinatal out-
before 20 weeks of gestation. We reviewed the charts come (stillbirth, neonatal death, respiratory support at
of 625 women without a diagnosis of chronic hyper- birth, arterial cord pH less than 7, 5-minute Apgar
tension to identify 476 women without chronic hyper- score 3 or less, and seizures) increased in frequency
tension who met inclusion criteria. across groups (P,.01; Table 3). After adjusting for
The three groups were significantly different prior preterm delivery and nulliparity, women with
regarding several baseline variables (Table 1). chronic hypertension and not using antihypertensive
Women without chronic hypertension were more medications were at increased risk for the adverse
likely to be younger, nulliparous, Hispanic, and have composite outcome compared with women with no
lower body mass indexes than either group with chronic hypertension (adjusted odds ratio [OR] 2.9,
chronic hypertension. Women without chronic hyper- 95% CI 1.21–6.85) as were women in the with chronic
tension were also less likely to have baseline renal hypertension on antihypertensive medication group
disease, gestational diabetes, or pregestational diabe- (adjusted OR 5.0, 95% CI 2.38–10.54; Table 3).
tes. As anticipated, women without a diagnosis of Although the incidence of stillbirth increased across
chronic hypertension had the lowest average systolic exposure groups (1.3% vs 1.9% vs 2.9%), this trend
and diastolic BPs throughout all three trimesters, was not statistically significant (P5.06) nor was it sig-
whereas women with chronic hypertension on medi- nificant in adjusted analyses. The incidence of neona-
cations had the highest BPs (Table 2). tal death (measured only in those with liveborn

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Table 2. Blood Pressure Characteristics Throughout Pregnancy

No Chronic Chronic Hypertension, Less Than 140/ Chronic Hypertension, Less Than
Hypertension 90 mm Hg, No Antihypertensive 140/90 mm Hg, Antihypertensive
Characteristic (n5476) Medication (n5212) Medications (n5618) P

BP (mm Hg) at less


than 20 wk
of gestation
Systolic 109610 12268 12668 ,.01
Diastolic 6467 7367 7567 ,.01
BP at 24–27 6/7
wk of
gestation
Systolic 109611 120611 124611 ,.01
Diastolic 6469 7068 7369 ,.01
Systolic 140 or 3 (0.6) 13 (6.1) 102 (16.5) ,.01
greater
Diastolic 90 or 1 (0.2) 2 (0.9) 62 (10.0) ,.01
greater
BP at 28–31 6/7
wk of
gestation
Systolic 110611 120611 125612 ,.01
Diastolic 6468 7067 7469 ,.01
Systolic 140 or 8 (1.7) 18 (8.5) 112 (18.1) ,.01
greater
Diastolic 90 or 1 (0.2) 4 (1.9) 58 (9.4) ,.01
greater
BP at 32–36 wk of
gestation
Systolic 111611 123612 128613 ,.01
Diastolic 6569 7368 76610 ,.01
Systolic 140 or 14 (2.9) 37 (17.5) 163 (26.4) ,.01
greater
Diastolic 140 8 (1.7) 13 (6.1) 109 (17.6) ,.01
or greater
BP, blood pressure.
Data are mean6SD or n (%) unless otherwise specified.

neonates) increased across the exposure groups medications were not more likely to develop pre-
(P5.03), but in adjusted analyses, the increased odds eclampsia or severe preeclampsia than women in the
was only significant for women receiving medication. no hypertension group. Women on medications were
Similarly, the incidence of preterm birth before 34 more likely to develop preeclampsia or severe
and 37 weeks of gestation increased across exposure preeclampsia.
groups, but the increased odds for early preterm birth
was significant only for women receiving medication DISCUSSION
after adjusting for confounding factors. The incidence In our cohort, 25% of women with a history of chronic
of SGA was significantly different between groups in hypertension were normotensive (BP less than
unadjusted analyses, but in adjusted analyses, the odds 140/90 mm Hg) before 20 weeks of gestation without
of SGA were significantly higher in those on antihy- receiving antihypertensive medication. Even so, these
pertensive medication compared with women without women were at increased of adverse perinatal out-
chronic hypertension. comes, including perinatal death, cord blood acid-
Any diagnosis of preeclampsia, severe preeclamp- emia, seizures, and respiratory support.
sia, and early-onset severe preeclampsia increased Ankumah et al performed a study similar as ours;
across groups (Table 4; P,.01). However, after adjust- in their cohort women with untreated hypertension
ing for significant confounding variables, women with and women using antihypertensive medication were
chronic hypertension not taking antihypertensive both more likely than women with no history of

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Table 3. Neonatal and Perinatal Outcomes

Chronic Chronic
Hypertension, Hypertension,
Less Than 140/ Less Than 140/
90 mm Hg, No 90 mm Hg,
No Chronic Antihypertensive Antihypertensive
Hypertension Medication RR AOR Medications RR AOR
Outcome (n5476) (n5212) (95% CI) (95% CI) (n5618) (95% CI) (95% CI) P*
Composite 14 (2.9) 21 (9.9) 3.4 2.9 90 (14.6) 5.0 5.0 ,.01
neonatal (1.7–6.5) (1.21–6.85) (2.9–8.6) (2.38–10.54)
outcome†
Perinatal death† 8 (1.7) 6 (2.8) 1.7 (0.6–4.8) 1.6 24 (3.9) 2.3 (1.0–5.1) 2.1 (0.90–4.72) .03
(stillbirth (0.54–4.65)
+neonatal
death)
Stillbirth‡ 6 (1.3) 4 (1.9) 1.5 (0.4–5.3) 1.5 18 (2.9) 2.3 (0.9–5.8) 2.2 .06
(0.40–5.26) (0.84–5.67)
Neonatal death§ 2/470 (0.4) 2/208 (1.0) 1.7 (0.4–7.5) 1.8 6/600 (1.0) 3.1 (1.0–9.2) 3.4 .03
(denominator (0.39–8.00) (1.12–10.36)
is live births)
Any respiratory 8 (1.7) 13 (6.3) 3.7 4.1 62 (10.4) 6.1 3.9 (1.36–11.4) ,.01
supportk (1.55–8.72) (1.17–.6) (2.95–12.59)
Cord blood 1/378 (0.3) 3/172 (1.8) — — 7/487 (1.4) — — .1
acidemia
5-min Apgar 0 1 (0.5) 8 (1.3) ,.01
score 3 or less
Seizures 0 5 (2.4) 5 (0.8) .16
Preterm birth at 68/470 (14.5) 60/208 (28.9) 2.0 (1.5–2.7) 1.7 (1.1–2.6) 236/600 (39.3) 2.7 (2.1–3.5) 2.4 (1.7–3.3) ,.01
less than 37
wk of
gestation¶
Preterm birth at 17/470 (3.6) 14/208 (6.7) 1.9 (0.9–3.7) 1.4 (0.6–3.0) 102/600 (17.0) 4.7 (2.9–7.7) 3.3 (1.8–5.9) ,.01
less than 34
wk of
gestation¶
Small for 73 (15.3) 24 (11.3) 0.7 (0.5–1.1) 0.9 (0.51– 111 (18.0) 1.2 (0.9–1.5) 1.8 (1.16–2.67) .20
gestational 1.68)
age#

RR, relative risk; AOR, adjusted odds ratio.


Data are n (%) or n/N (%) unless otherwise specified.
Composite neonatal outcome: any one of stillbirth, neonatal death, continuous positive airway pressure, ventilator, umbilical cord pH less
than 7, 5-min Apgar score 3 or less, seizures. Total of individual components is greater than the number of outcomes because they are not
mutually exclusive. Not all patients had documented cord blood gas. Denominator for neonatal death and preterm birth at less than 35
weeks of gestation was live births.
* P value based on x2 test for trend.

Adjusted for age, prior preterm delivery, race, body mass index, diabetes, baseline renal disease, and nulliparity.

Adjusted for prior preterm delivery, nulliparity.
§
Adjusted for prior preterm delivery, nulliparity.
k
Adjusted for gestational age at delivery.

Adjusted for prior preterm delivery, race, diabetes, baseline renal disease, and nulliparity.
#
Adjusted for race, body mass index, tobacco use, and diabetes.

chronic hypertension to experience preterm delivery, but did not distinguish by whether they were on
growth restriction, and preeclampsia.13 However, medication.
these data did not report BPs during pregnancy. The strengths of this study include the a priori
Su et al14 demonstrated that women with untreated determination of sample size needed for the primary
hypertension had an increased risk of preterm birth outcome. We collected detailed data on a large cohort
and SGA compared with those without chronic hyper- of women with chronic hypertension, allowing us to
tension. However, no data were available on baseline clearly identify a population of women with chronic
BPs during pregnancy. Ankumah et al13 in a second- hypertension who have BPs less than 140/90 mm Hg
ary analysis found the lowest risk of adverse outcomes without medications for whom there is a paucity of
in normotensive chronic hypertensive women at base- published information. All patients had documented
line compared with those with elevated baseline BPs, BPs before 20 weeks of gestation enabling us to

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Table 4. Maternal Outcomes

Chronic Chronic
Hypertension, Less Hypertension, Less
Than 140/90 mm Than 140/90 mm
Hg, No Hg,
No Chronic Antihypertensive Antihypertensive
Hypertension Medication RR AOR Medications RR (95% AOR
Outcome (n5476) (n5212) (95% CI) (95% CI) (n5618) CI) (95% CI) P*
Any 30 (6.3) 29 (13.7) 2.2 1.5† 162 (26.2) 4.2 3.3 ,.01
preeclampsia (1.3–3.5) (0.86–2.79) (2.9–6.0) (2.07–5.18)
diagnosis
Severe 13 (2.7) 15 (7.1) 2.6 1.6† 106 (16.7) 6.1 4.0 ,.01
preeclampsia (1.3–5.3) (0.72–3.71) (3.5–10.7) (2.08–7.55)
Early-onset 0 2 (1.0) — — 45 (7.3) — — ,.01
severe
preeclampsia

RR, relative risk; AOR, adjusted odds ratio; —, not calculated as a result of 0 cases in the reference group.
Data are n (%) unless otherwise specified.
* P value based on x2 test for trend.

Adjusted for history of preeclampsia, diabetes, baseline renal disease, and nulliparity.

distinguish between chronic hypertension and pre- preterm birth before 34 weeks of gestation, we had
eclampsia; additionally, all women included in the approximately 35% power to detect a 50% reduction in
hypertension groups had a confirmed diagnosis of the risk in women without hypertension compared with
chronic hypertension. Women with a history of “pre- the no medication group. We had more than 80%
hypertension” or hypertension that resolved after power to detect a difference of a 50% reduction for
weight loss surgery were excluded from the study. preeclampsia.
One of the limitations of this study is that the In summary, we found that women with a history
sample is from a single academic institution and of chronic hypertension who are normotensive with-
therefore may not be generalizable to other institutions. out antihypertensive medication before 20 weeks of
Specifically, our cohort was largely black, obese, and gestation are at increased risk of adverse perinatal
had a high incidence of pregestational diabetes. Addi- outcomes compared with women without a diagnosis
tionally, women with chronic hypertension were differ- of chronic hypertension.
ent than women without chronic hypertension in several
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