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OBSTETRICS

Prevalence, trends, and outcomes of chronic hypertension:a nationwide sample of delivery admissionsBrian T. Bateman, MD; Pooja Bansil, MPH; Sonia Hernandez-Diaz, MD, DrPH; Jill M. Mhyre, MD;William M. Callaghan, MD, MPH; Elena V. Kuklina, MD, PhD

OBJECTIVE: We sought to define the prevalence, trends, and outcomesof primary and secondary chronic hypertension in a population-basedsample of deliveries.

STUDY DESIGN: An estimated 56,494,634 deliveries were identifiedfrom the 1995 through 2008 Nationwide Inpatient Sample. The associ-ation of primary and secondary chronic hypertension with adverse fetaland maternal outcomes was evaluated using regression modeling andadjusted population-attributable fractions were calculated.

RESULTS: During the study period, the prevalence of primary andsecondary hypertension increased from 0.90% in 1995 through
1996 to 1.52% in 2007 through 2008 (P for trend � .001) and from
admissions. Am J Obstet Gynecol 2012;206:134.e1-8.

134.e1 American Journal of Obstetrics & Gynecology FEBRUARY 2012

0.07% to 0.24% (P for trend � .001), respectively. The population-attributable fraction for chronic hypertension was considerable formany maternal adverse outcomes, including acute renal failure(21%), pulmonary edema (14%), preeclampsia (11%), and in-hos-pital mortality (10%).

CONCLUSION: Primary and secondary chronic hypertension were bothstrongly associated with adverse pregnancy outcomes and accountedfor a substantial fraction of maternal morbidity. Prioritizing research ef-forts in this area is needed.

Key words: chronic hypertension, epidemiology, obstetric
complications
Cite this article as: Bateman BT, Bansil P, Hernandez-Diaz S, et al. Prevalence, trends, and outcomes of chronic hypertension: a nationwide sample of delivery

Chronic hypertension is a relativelycommon comorbidity in pregnancy1-3

and a well-established risk factor for a num-ber of adverse perinatal outcomes, includingpreterm birth,4,5 perinatal death,5-8 and in-rauterine growth restriction,4,5 as well as

adverse maternal outcomes, includingpreeclampsia,4,5,9,10 stroke,8,11,12 acute re-nal failure,8,11 pulmonary edema,8,11 and

aternal death.8,11 Although the majority

From the Division of Obstetric Anesthesia, DeMedicine, Massachusetts General Hospital, HDepartment of Epidemiology, Harvard SchooBoston, MA; the Divisions of Heart Disease anKuklina) and Reproductive Health (Dr CallagPrevention and Health Promotion, Centers foand the Department of Anesthesiology, UniveMI (Dr Mhyre).

Received Aug. 24, 2011; revised Oct. 11, 2011;

The authors report no conflict of interest.

The findings and conclusions in this report are threpresent the official position of the Centers for D

Reprints: Brian T. Bateman, MD, Division of ObsCritical Care, and Pain Medicine, MassachusettFruit St., Boston, MA 02114. BBateman@partne

0002-9378/free • © 2012 Mosby, Inc. All rights

For Editors’ Commentary, see Table

of chronic hypertension among pregnantwomen is due to primary hypertension,about 10% of cases occur secondary toother medical conditions, such as diabetesmellitus, chronic renal disease, thyroid dis-ease, and collagen vascular disease.13

There are few population-based stud-ies examining the impact of chronic hy-

rtment of Anesthesia, Critical Care, and Painard Medical School (Dr Bateman), and thePublic Health (Dr Hernandez-Diaz),troke Prevention (Ms Bansil and Dr), National Center for Chronic Diseaseisease Control and Prevention, Atlanta, GA;y of Michigan Health System, Ann Arbor,

epted Oct. 31, 2011.

of the authors and do not necessarilyase Control and Prevention.

ic Anesthesia, Department of Anesthesia,neral Hospital, Harvard Medical School, 55

org.

erved. • doi: 10.1016/j.ajog.2011.10.878

ontents

pertension on obstetric outcomes in theUnited States8,11; this is particularly truefor chronic hypertension that is second-ary to or associated with other condi-tions. As the prevalence of advanced ma-ternal age14 and obesity15 increase amongchildbearing women in the United States,both primary and secondary chronic hy-pertension are likely to become an increas-ingly common obstetric conditions.

The purpose of this study is 3-fold: (1) toexamine nationwide trends in the preva-lence of primary and secondary chronichypertension during delivery hospitaliza-tions in the United States; (2) to assess theeffect of primary and secondary chronichypertension on fetal and maternal obstet-ric complications; and (3) during the mostrecent years in the study period, to estimatethe contribution of primary and secondarychronic hypertension to the burden of se-lect fetalandmaternalcomplications in theUnited States.

MATERIALS AND METHODSHospital discharge data were obtainedfrom the Nationwide Inpatient Sample(NIS), part of the Healthcare Cost andUtilization Project, a federal-state-in-

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Bateman. Chronic hypertension: a nationwide sample of delivery admissions. Am J Obstet Gynecol 2012.

www.AJOG.org Obstetrics Research

FEBRUARY 2012 Americ

Agency for Healthcare Research andQuality. The NIS is a 20% stratified sam-ple of all US community hospitals as de-fined by the American Hospital Associa-tion: nonfederal, short-term, general,and specialty hospitals whose facilitiesare open to the public. To create a samplethat is maximally representative of all UScommunity hospital admissions, hospi-tal are selected for inclusion in the NISbased on 5 characteristics: rural/urbanlocation, number of beds, region of thecountry, teaching status, and ownership.The NIS includes all discharges from thesampled hospitals and includes between5-8 million discharges from an averageof 1000 hospitals each year.16 Further in-ormation about the methodology used toreate the dataset is available at http://ww.hcup-us.ahrq.gov/nisoverview.jsp.Our analysis included all delivery hospi-

alizations of women aged �15 years from995 through 2008; those who had abor-ions, ectopic pregnancies, or molar preg-ancies were excluded from the analyses.elivery hospitalizations were identifiedsing a validated approach that selects ad-issions with relevant diagnosis-related

roups and International Classification ofiseases, Ninth Revision, Clinical Modifica-

ion (ICD-9-CM) diagnosis/procedureodes, as previously described.17 In addi-ion, ICD-9-CM codes were used to classifyospitalizations with chronic hypertension,ssociated comorbidities, and maternal andetal outcomes (Appendix).

Data management and statistical analysesere conducted using SAS (SAS Inc, Cary,C) and SAS-callable SUDAAN software

version 9.2, RTI International, Researchriangle, NC) to account for the stratified

ampling design used to collect the hospitalischarge data. We used �2 tests with a sig-

nificance level of .05 to compare thedistribution of deliveries with and withoutchronic hypertension by sociodemographicand hospital characteristics and maternal co-morbidities. For purposes of analysis, sec-ondary hypertension was defined as chronichypertension in association with conditionsthat can cause hypertension through eithervascular or endocrinologic mechanisms in-cluding pregestational diabetes, chronicrenal disease, collagen vascular disease (in-cludingsystemiclupuserythematous,sclero-

TABLE 1Patient characteristics, comparing thosewith and without chronic hypertension

Characteristic

With chronichypertension(N � 731,694), n (%)

Without chronichypertension(N � 55,762,940), n (%) Pa value

Age, y.....................................................................................................................................................................................................................................

�20 23,094 (3.2) 6,236,678 (11.2) � .001.....................................................................................................................................................................................................................................

20–34 478,006 (65.3) 41,889,300 (75.1).....................................................................................................................................................................................................................................

�35 230,594 (31.5) 7,637,061 (13.7)..............................................................................................................................................................................................................................................

Primary payer.....................................................................................................................................................................................................................................

Publicb 258,620 (35.4) 21,254,523 (38.2) � .001.....................................................................................................................................................................................................................................

Private (including HMO) 432,453 (59.3) 30,752,962 (55.3).....................................................................................................................................................................................................................................

Other (including self-pay) 38,693 (5.3) 3,596,175 (6.5)..............................................................................................................................................................................................................................................

Multiple birth.....................................................................................................................................................................................................................................

Yes 18,384 (2.5) 919,225 (1.7) � .001.....................................................................................................................................................................................................................................

No 713,304 (97.5) 54,843,715 (98.3)..............................................................................................................................................................................................................................................

Previous cesarean delivery.....................................................................................................................................................................................................................................

Yes 156,303 (21.4) 7,374,516 (13.2) � .001.....................................................................................................................................................................................................................................

No 575,391 (78.6) 48,388,423 (86.8)..............................................................................................................................................................................................................................................

Pregestational diabetes.....................................................................................................................................................................................................................................

Yes 48,263 (6.6) 364,907 (0.7) � .001.....................................................................................................................................................................................................................................

No 683,431 (93.4) 55,398,031 (99.3)..............................................................................................................................................................................................................................................

Chronic renal disease.....................................................................................................................................................................................................................................

Yes 6614 (0.9) 84,866 (0.2) � .001.....................................................................................................................................................................................................................................

No 725,080 (99.1) 55,678,074 (99.8)..............................................................................................................................................................................................................................................

Collagen vascular disease.....................................................................................................................................................................................................................................

Yes 4482 (0.6) 49,520 (0.1) � .001.....................................................................................................................................................................................................................................

No 727,212 (99.4) 55,713,420 (99.9)..............................................................................................................................................................................................................................................

Pheochromocytoma.....................................................................................................................................................................................................................................

Yes c c .32.....................................................................................................................................................................................................................................

No c 55,762,940 (100.0)..............................................................................................................................................................................................................................................

Hyperplasia of renal artery.....................................................................................................................................................................................................................................

Yes c c .05.....................................................................................................................................................................................................................................

No c c

..............................................................................................................................................................................................................................................

Hyperaldosteronism.....................................................................................................................................................................................................................................

Yes 158 (0.02) 558 (0.001) � .001.....................................................................................................................................................................................................................................

No 731,537 (99.9) 55,762,382 (100.0)..............................................................................................................................................................................................................................................

Cushing syndrome.....................................................................................................................................................................................................................................

Yes c 412 (0.001) � .001.....................................................................................................................................................................................................................................

No c 55,762,529 (100.0)..............................................................................................................................................................................................................................................

Thyroid disorders.....................................................................................................................................................................................................................................

Yes 29,810 (4.1) 772,032 (1.4) � .001.....................................................................................................................................................................................................................................

No 701,885 (95.9) 54,990,908 (98.6)..............................................................................................................................................................................................................................................

Maternal coarctation of aorta.....................................................................................................................................................................................................................................

Yes 130 (0.02) 684 (0.001) � .001.....................................................................................................................................................................................................................................

No 731,565 (99.9) 55,762,257 (100.0)..............................................................................................................................................................................................................................................

HMO, health maintenance organization; RSE, residual standard error.a �2; b Including Medicaid and Medicare; c Number too small to report stable estimate (n �10 and/or RSE �0.30).

derma, and other diffuse diseases of connec-

an Journal of Obstetrics & Gynecology 134.e2

http://www.hcup-us.ahrq.gov/nisoverview.jsp

http://www.hcup-us.ahrq.gov/nisoverview.jsp

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Research Obstetrics www.AJOG.org

tive tissue), thyroid disorders, pheo-chromocytoma, hyperplasia of the renal ar-tery, Cushing syndrome, hyperaldosteron-ism, and maternal coarctation of the aorta.Primaryhypertensionwasdefinedaschronichypertension without any of these associatedcomorbidities. To examine trends, the age-standardized prevalence of overall, primary,and secondary chronic hypertension, as wellas chronic hypertension with selected indi-vidual comorbidities, were computed for2-year intervals.Estimateswerestandardizedby the age distribution of delivery hospital-izations for the last 2 years (2007 through2008) and applying this distribution to theformer 2-year intervals.

Giventheincreasingprevalenceofchronichypertension, we restricted our analyses ofthe effect of overall chronic hypertension,primaryhypertension,andsecondaryhyper-tension on fetal and maternal outcomes tothe last 2 years of the study period (2007through2008).Frequenciesper1000deliver-ies were calculated for fetal outcomes (still-birth, poor fetal growth, spontaneous deliv-ery �37 weeks of gestation) and maternal

utcomes (preeclampsia, stroke/cerebrovas-ular complications, acute renal failure, pul-onary edema, mechanical ventilation, ce-

arean delivery, length of hospital stay �6ays [corresponding to approximately the8th percentile for length of stay], and in-ospital mortality), stratified by all-cause,rimary, and secondary chronic hyperten-ionstatus.Logisticregressionwasusedtoes-imate odds ratios (ORs) and respective 95%onfidenceintervalsofmaternalandfetalde-ivery outcomes by maternal chronic hyper-ension status, while adjusting for multipleirths,yearof study, insurancestatus, region,nd age; the models for cesarean deliveryere additionally adjusted for previous ce-

arean delivery and the models for length oftay included adjustment for admission andisposition status. To estimate the burden ofisease at the population level, population-ttributable fractions for chronic hyperten-ion (overall), primary hypertension, andecondary hypertension for each of the fetalnd maternal outcomes of interest were cal-ulatedusingadjustedORasestimatesofrel-tive risk, as described elsewhere.18 The pop-lation-attributable fraction estimates theroportion of disease that would be elimi-ated if the exposure, in this case chronic hy-
ertension, could be eliminated.
134.e3 American Journal of Obstetrics & Gynecolo

A similar analysis was conducted ex-mining the association of chronic hy-ertension with the comorbidities mostommonly associated with chronic hyper-

FIGURE 1Trends in the rate of chronic hyper

ateman. Chronic hypertension: a nationwide sample of deli

FIGURE 2Trends in the rate of chronic hyperwith comorbidities: 1995 to 2008

0

0.02

0.04

0.06

0.08

0.1

0.12

0.14

0.16

1995-1996 1997-1998 1999-2000

Percen

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Chronic Hypertension with pre-gesta�onal diabetes

Chronic Hypertension with collagen vascular disease

ateman. Chronic hypertension: a nationwide sample of deli

gy FEBRUARY 2012

ension–pregestational diabetes, chronicenal disease, collagen vascular disease,nd thyroid disorders–and selected fetal/aternal outcomes. Because of the rela-

sion: 1995 to 2008

admissions. Am J Obstet Gynecol 2012.

sion

1-2002 2003-2004 2005-2006 2007-2008

Years

Chronic Hypertension with chronic renal disease

Chronic Hypertension with thyroid disorders

admissions. Am J Obstet Gynecol 2012.

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tively small numbers of patients withchronic hypertension and the comorbidi-ties considered, the NIS for the entire studyperiod (1995 through 2008) was used forthis analysis to ensure adequate power tomake reliable estimates of risk.

RESULTSFrom 1995 through 2008, an estimated56,494,634 delivery hospitalizations wereidentified, of which 731,694 were classifiedas deliveries with chronic hypertension. Ofthe patients with chronic hypertension,649,899 (88.8%) had primary hyperten-sion and 81,795 (11.2%) had secondaryhypertension; in the final 2 years of thestudy period (2007 through 2008), of the153,570 patients with chronic hyperten-sion, 132,808 (86.5%) had primary hyper-tension and 20,762 (13.5%) had secondaryhypertension. Compared to women withdelivery hospitalizations without chronichypertension, those with chronic hyper-tension were older, and had higher rates ofmultiple birth, previous cesarean delivery,pregestational diabetes, chronic renal dis-ease, collagen vascular disease, hyperaldo-steronism, Cushing disease, thyroid dis-

TABLE 2Frequency (SE) per 1000 deliveries, oand maternal complications: 2007-2

VariableWithout chronichypertension

Fetal outcomes..........................................................................................................

Stillbirth 6.0 (0.01)..........................................................................................................

Poor fetal growth 18.8 (0.4)..........................................................................................................

Spontaneous delivery�37 wk gestation

74.0 (0.1)

...................................................................................................................

Maternal outcomes..........................................................................................................

Preeclampsia 35.4 (0.7)..........................................................................................................

Stroke/cerebrovascularcomplications

0.4 (0.02)

..........................................................................................................

Acute renal failure 0.4 (0.02)..........................................................................................................

Pulmonary edema 0.2 (0.01)..........................................................................................................

Mechanical ventilation 0.5 (0.02)..........................................................................................................

Cesarean delivery 323.3 (0.3)..........................................................................................................

Length of stay �6 d 13.6 (0.5)..........................................................................................................

In-hospital mortality 0.1 (0.01)...................................................................................................................

RSE, residual standard error.a Number too small to report stable estimate (n �10 and/or R

Bateman. Chronic hypertension: a nationwide sample of d

ease, and maternal coarctation of the aorta

(all P � .001) (Table 1). Themostcommoncomorbidities associated with chronic hy-pertension included pregestational diabetes(present in6.6%ofchronichypertensionad-missions), thyroid disorders (present in4.1%), chronic renal disease (present in0.9%),andcollagenvasculardisease(presentin 0.6%).

The age-adjusted prevalence of all-causechronic hypertension increased signifi-cantly throughout the seven 2-year inter-vals, from 1.01% in 1995 through 1996 to1.76% in 2007 through 2008 (P for trend�.001) (Figure 1). The prevalence of pri-mary hypertension increased from 0.90%to 1.52% (P � .001) and of secondary hy-

ertension from 0.07% to 0.24% (P �001). Significant increasing trends werelso observed for chronic hypertensionith pregestational diabetes, chronic renalisease, collagen vascular disease, and thy-oid disorders (all P � .001) (Figure 2).

The frequency of considered adversefetal and maternal outcomes were uni-formly higher for delivery hospitaliza-tions with overall, primary, and second-ary hypertension (Table 2). As comparedto delivery hospitalizations without chronic

etal

ith chronicypertensionverall)

Primaryhypertension

Secondaryhypertension

..................................................................................................................

15.1 (0.7) 14.1 (0.7) 21.1 (2.3)..................................................................................................................

53.9 (1.9) 54.3 (2.0) 51.5 (3.7)..................................................................................................................

93.1 (5.0) 183.8 (4.6) 252.2 (9.6)

..................................................................................................................

..................................................................................................................

68.3 (5.0) 264.0 (5.0) 295.8 (8.9)..................................................................................................................

2.7 (0.3) 2.2 (0.3) 2.8 (0.8)

..................................................................................................................

5.9 (0.5) 4.2 (0.4) 16.7 (2.2)..................................................................................................................

1.5 (0.3) 1.4 (0.2) a..................................................................................................................

3.8 (0.4) 3.5 (0.4) 6.3 (1.3)..................................................................................................................

61.7 (4.9) 543.1 (5.1) 680.2 (7.7)..................................................................................................................

95.9 (3.8) 86.7 (3.3) 154.6 (9.1)..................................................................................................................

0.4 (0.1) a a

..................................................................................................................

0.30).

ery admissions. Am J Obstet Gynecol 2012.

hypertension, those with primary hyper- p

FEBRUARY 2012 Americ

tension had an OR of 2.2 for stillbirth, 3.0for poor fetal growth, and 2.9 for sponta-neous delivery �37 weeks’ gestation (Ta-ble 3). For adverse maternal outcomes, theOR associated with primary hypertensionwere �5 in all categories with the excep-tion of cesarean delivery. For secondaryhypertension, the effects on outcomeswere even more profound, particularly ad-verse maternal outcomes; the OR for mostadverse maternal outcome were �10, in-luding maternal mortality which was 13.2Table 3). The population-attributableractions for overall chronic hypertensionere substantial for many maternal ad-erse outcomes; principal among theseere acute renal failure (21%), pulmonary

dema (14%), preeclampsia (11%), andn-hospital mortality (10%) (Table 3).

In Table 4, an analysis of the interaction ofhronichypertensionandselectedassociatedomorbidities is presented (compared to aeferencegroupthatincludeddeliveryhospi-alizations without chronic hypertensionnd without the comorbidity of interest).he combinations of chronic hypertensionith chronic renal disease, collagen vascularisease, or pregestational diabetes were par-icularly detrimental. The combination ofhyroid disease and chronic hypertensionenerallydidnotresultingreatlyelevatedriskbove what was observed for hypertensionlone.

COMMENTChronic hypertension is a well-recognizedrisk factor for many adverse pregnancyoutcomes and has been previously re-ported to be increasing in prevalenceamong delivery hospitalizations in theUnited States.11 Our 14-year study usinghe largest discharge data set available inhe United States, the NIS, finds that theverall prevalence of chronic hypertensionmong delivery hospitalizations showsustained increase (approximately 80%cross the study period) such that 1.8% ofelivery hospitalizations were complicatedy chronic hypertension in 2007 through008, and confirms and quantifies the rolef chronic hypertension in mediating aange of adverse fetal and maternal out-omes. Our study also demonstrates thatecondary hypertension has increased in

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1996 to 0.24% in 2007 through 2008 (ap-proximately 300% increase) and has a par-ticularly strong,detrimentaleffectonpreg-nancy outcomes.

Consistent with previously publishedstudies,19-22 we found that chronic hyper-tension increased the risk of stillbirth byapproximately 2.3-fold. In our study, theOR for stillbirth increased dramaticallywhen chronic hypertension occurred in thesetting of certain comorbid conditions–itwas �4 for chronic hypertension with di-betes and �7 for chronic renal diseasend collagen vascular disease. Similar pat-erns of associations were observed foroor fetal growth, also in a line with previ-usly published reaserch.4,5,20 The syner-istic effects of chronic hypertension andhese comorbid conditions may be ex-lained by vasculopathy leading to aoorly perfused placenta and/or acceler-ted placenta aging. Alternatively, it maye an iatrogenic effect of treatment of theypertension; a metaanalysis of treatmentf mild to moderate hypertension suggestshat treatment-associated decrease in

TABLE 3Estimated ORs and PAFs of fetal an

Variable

With chronic hyperte

ORa (95% CI)

Fetal outcomes..........................................................................................................

Stillbirthc 2.31 (2.11–2.53)..........................................................................................................

Poor fetal growthc 3.00 (2.83–3.19)..........................................................................................................

Spontaneous delivery�37 wk gestationc

3.01 (2.88–3.14)

...................................................................................................................

Maternal outcomes..........................................................................................................

Preeclampsiac 10.07 (9.68–10.48)..........................................................................................................

Stroke/cerebrovascularcomplicationsc

5.41 (4.27–6.86)

..........................................................................................................

Acute renal failurec 14.62 (12.06–17.73)..........................................................................................................

Pulmonary edemac 9.26 (6.67–12.85)..........................................................................................................

Ventilationc 6.33 (5.12–7.83)..........................................................................................................

Cesarean deliveryd 2.54 (2.46–2.64)..........................................................................................................

Length of stay �6 de 6.73 (6.21–7.29)..........................................................................................................

In-hospital mortalityc 6.20 (3.33–11.54)...................................................................................................................

Secondary hypertension includes chronic hypertension with psyndrome, hyperaldosteronism, hyperplasia of the renal arteryCI, confidence interval; OR, odds ratio; PAF, population-attributo risk factor (chronic hypertension status) and RR � relativea Referent group: without chronic hypertension; b Referent gro

d Adjusted for previous cesarean delivery, multiple birth, yeastatus, region, and age.

Bateman. Chronic hypertension: a nationwide sample of d

ean arterial pressure is associated with c


ompromised fetal growth.23 Interest-ngly, pregestational diabetes mitigated theffect of hypertension on poor fetalrowth; it is well known that diabetes in-reases fetal size and predisposes to macro-omia24 and this may be the mechanism.

Consistent with its shared etiology ofoor placentation, the risk of preeclamp-ia follows a similar pattern with what isbserved in stillbirth and poor fetalrowth– chronic hypertension by itself isignificantly associated with preeclamp-ia, but markedly more so when concur-ent with chronic renal disease or colla-en vascular disease. At the most severend of the spectrum of adverse maternalutcomes, stroke/cerebrovascular compli-ation, acute renal failure, pulmonarydema, mechanical ventilation, and death,he synergistic detrimental effect of theombination of chronic hypertension andssociated conditions becomes even morerofound. This marked increase in risk ofdverse maternal outcomes for patientsith chronic hypertension and these asso-

iated illnesses should factor both into pre-

maternal complications: 2007-2008

n (overall) Primary hypertension

(95% CI) ORb (95% CI) PAF (95% C

.........................................................................................................................

44 (1.99–2.90) 2.23 (2.02–2.48) 1.93 (1.52.........................................................................................................................

26 (2.89–3.64) 3.05 (2.87–3.25) 2.86 (2.54.........................................................................................................................

99 (2.72–3.25) 2.89 (2.77–3.02) 2.41 (2.20

.........................................................................................................................

.........................................................................................................................

78 (10.15–11.41) 10.18 (9.77–10.60) 9.19 (8.67.........................................................................................................................

49 (5.30–9.77) 5.37 (4.10–7.04) 6.24 (4.16

.........................................................................................................................

02 (17.13–24.95) 13.14 (10.57–16.33) 12.90 (10.1.........................................................................................................................

12 (9.34–19.06) 8.99 (6.40–12.64) 10.89 (6.96.........................................................................................................................

76 (7.33–12.28) 6.22 (4.90–7.88) 7.56 (5.43.........................................................................................................................

83 (1.69–1.98) 2.39 (2.31–2.48) 1.47 (1.36.........................................................................................................................

55 (8.78–10.33) 6.49 (5.96–7.07) 7.42 (6.80.........................................................................................................................

44 (3.43–18.23) 5.49 (2.60–11.58) 7.23 (1.34.........................................................................................................................

stational diabetes mellitus, chronic renal disease, collagen vascrctation of aorta.fraction [PAF � pd (RR – 1/RR), where pd � proportion of case

or outcome for exposed compared with unexposed].

ithout chronic hypertension and select comorbidities; c Adjustedtudy, insurance status, region, and age; e Adjusted for dispositio

ery admissions. Am J Obstet Gynecol 2012.

onceptional counseling regarding the a

gy FEBRUARY 2012

isks of pregnancy and the approach to theanagement of pregnancy and delivery. Inany circumstances, patients with these

onditions should be cared for by a high-isk obstetric specialist and delivered inospital settingswhere intensityofcarecane rapidly escalated if needed.We used standard methodology to cal-

ulate population-attributable fractions ofhronic hypertension for a range of ad-erse pregnancy outcomes.18 Assuminghat the associations are causal and chronicypertension removable, population-at-ributable fractions estimate the propor-ion of the adverse outcomes in the popu-ation that would be prevented if chronicypertension or its effects could be ne-ated. Although causality cannot be estab-ished in our cross-sectional study, the cal-ulated population-attributable fractionstimates suggest that chronic hyperten-ion may be responsible for �10% of theopulation burden of preeclampsia, acuteenal failure, pulmonary edema, mechan-cal ventilation, prolonged hospitalization,

Secondary hypertension

ORb (95% CI) PAF (95% CI)

..................................................................................................................

5) 3.23 (2.57–4.06) 0.56 (0.36–0.78)..................................................................................................................

0) 2.92 (2.52–3.38) 0.42 (0.31–0.53)..................................................................................................................

2) 4.36 (3.98–4.79) 0.61 (0.52–0.69)

..................................................................................................................

..................................................................................................................

1) 11.92 (10.98–12.95) 1.63 (1.45–1.82)..................................................................................................................

2) 6.71 (3.88–11.61) 1.29 (0.42–2.26)

..................................................................................................................

5.72) 51.07 (37.60–69.38) 8.43 (5.80–11.08)..................................................................................................................

.97) 16.20 (8.82–29.75) 3.36 (1.09–5.73)

..................................................................................................................

6) 10.67 (7.13–15.98) 2.34 (1.21–3.53)..................................................................................................................

9) 4.37 (4.03–4.74) 0.38 (0.34–0.42)..................................................................................................................

5) 11.83 (10.28–13.62) 2.24 (1.92–2.56)..................................................................................................................

.15) 13.21 (4.92–35.43) 3.34 (–0.28 to 7.40)

..................................................................................................................

disease, pheochromocytoma, thyroid disorders, Cushing

spitalizations with maternal and fetal outcomes) exposed

ultiple birth, year of study, insurance status, region, and age;tus, admission status, multiple birth, year of study, insurance

d

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PAF I)

......... .........

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3. –3.2......... .........

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7. –8.4

......... .........

21. 2–1......... .........

14. –14......... .........

9. –9.7......... .........

1. –1.5......... .........

9. –8.0......... .........

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up: w for mr of s n sta

nd maternal death.

TABLE 4ORs for fetal and maternal complications: 1995-2008

Pregestational diabetes Chronic renal disease Collagen vascular disease Thyroid disorders

VariableWith chronichypertension

Without chronichypertension

With chronichypertension






Fetal outcomes...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Stillbirtha 4.30 (3.81–4.85) 3.05 (2.88–3.23) 7.29 (5.59–9.52) 1.74 (1.51–2.02) 7.42 (5.37–10.25) 2.74 (2.35–3.20) 1.86 (1.48–2.33) 0.98 (0.92–1.05)...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Poor fetal growtha 2.66 (2.40–2.94) 1.20 (1.14–1.27) 7.94 (6.67–9.44) 2.29 (2.12–2.49) 7.99 (6.44–9.91) 3.87 (3.55–4.22) 3.59 (3.20–4.02) 1.29 (1.25–1.34)...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Spontaneous delivery�37 wk gestationa

4.88 (4.63–5.15) 2.90 (2.83–2.98) 8.60 (7.64–9.67) 2.25 (2.15–2.35) 7.19 (6.22–8.30) 3.15 (2.98–3.33) 3.24 (3.02–3.48) 1.24 (1.21–1.27)

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Maternal outcomes...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Preeclampsiaa 13.96 (13.29–14.66) 3.80 (3.69–3.91) 27.87 (24.85–31.25) 3.28 (3.10–3.47) 17.41 (15.09–20.09) 2.96 (2.76–3.18) 9.74 (9.15–10.35) 1.38 (1.35–1.42)...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Stroke/cerebrovascularcomplicationsa

7.14 (4.90–10.40) 1.85 (1.41–2.44) 13.73 (6.63–28.44) 3.52 (2.34–5.31) 23.00 (11.47–46.14) 7.60 (5.26–10.97) 3.87 (2.07–7.23) 1.58 (1.29–1.94)

...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Acute renal failurea 35.41 (28.39–44.16) 4.43 (3.57–5.48) 253.4 (199.5–321.9) 62.40 (54.37–71.63) 191.5 (141.4–259.4) 12.60 (8.88–17.88) 14.17 (9.65–20.82) 1.27 (0.97–1.65)...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Pulmonary edemaa 11.97 (7.86–18.24) 4.01 (3.07–5.25) 23.29 (10.32–52.56) 9.06 (5.84–14.06) 15.52 (4.92–48.95) 6.08 (3.46–10.69) 9.85 (5.64–17.19) 1.54 (1.16–2.05)...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Ventilationa 11.87 (9.22–15.26) 3.34 (2.80–4.00) 19.29 (11.36–32.76) 8.25 (6.43–10.60) 26.20 (15.04–45.63) 11.09 (8.46–14.52) 5.71 (3.69–8.86) 1.84 (1.55–2.18)...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Cesarean deliveryb 5.75 (5.46–6.05) 3.33 (3.26–3.41) 5.73 (5.03–6.53) 1.74 (1.68–1.81) 4.38 (3.74–5.12) 1.89 (1.80–1.98) 3.16 (2.97–3.36) 1.27 (1.25–1.29)...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Length of stay �6 dc 14.74 (13.68–15.89) 5.34 (5.09–5.60) 42.16 (36.78–48.32) 6.52 (6.12–6.95) 30.29 (25.45–36.04) 6.18 (5.69–6.71) 8.40 (7.60–9.28) 1.77 (1.71–1.84)...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

In-hospital mortalitya 6.02 (2.71–13.40) 2.58 (1.59–4.17) 27.02 (8.72–83.73) 6.88 (3.56–13.29) 88.81 (41.90–188.2) 23.81 (14.67–38.66) 1.74 (0.24–12.40) 1.72 (1.06–2.77)............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

For each analysis, reference group was delivery admissions without chronic hypertension and without comorbidity of interest. Admissions with chronic hypertension but without comorbidity of interest was included as a group in each analysis. Because of similarityof estimates of association in these groups to those obtained when analyzing effect of overall chronic hypertension (Table 3), results are not shown.a Adjusted for multiple birth, year of study, insurance status, region, and age; b Adjusted for previous cesarean delivery, multiple birth, year of study, insurance status, region, and age; c Adjusted for disposition status, admission status, multiple birth, year of study,

insurance status, region, and age.


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Our study has certain limitations inherentin its methodology. The identification of co-morbiditiesandfetalandmaternaloutcomesis largely dependent on ICD-9-CM codescollected for billing purposes and thus is sus-ceptible to underascertainment or misclassi-fication bias. Similarly, because we are onlyable to examine hospital admissions, ouranalysis of the role of chronic hypertension isconfined to outcomes associated with deliv-ery. If a patient had mild hypertension priorto pregnancy and it was no longer an activeclinical issue at the time of delivery, it is likelythatthepatientwouldnotbecodedashavingchronic hypertension, which would cause usto underestimate the incidence and overesti-mate the effect of hypertension. Further, wedefine secondary hypertension as chronichypertension in the presence of comorbidi-ties that can cause hypertension throughvascular or endocrinologic mechanisms.However, we cannot definitively determinewhether the hypertension is secondary to thecomorbid condition or essential hyperten-sion with associated comorbidity; in eithercase, the point remains that chronic hyper-tension associated with certain conditionsidentifies a group at remarkably high risk ofadverse pregnancy outcomes. There are alsocertainpotentialconfounders, includingraceand body mass index, associated with bothchronic hypertension and adverse maternaland fetal outcomes, that we are unable to ad-just for in our analysis because they are notwell captured in our data set. Last, we do nothave information on the severity of patients’chronichypertensionandwhatmedications,if any, were used to control it–both of whichare likely tohaveanimportantrole intheriskof adverse outcomes. Despite these limita-tions, there are few population-based studiesexamining the role of chronic hypertensionin pregnancy outcome and our findings helpaddress this deficit. Further, the size of ourcohort allows us to carefully examine the in-teraction of chronic hypertension and rela-tively rare associated comorbidities with arange of outcomes, including some that areinfrequent and severe.

Inconclusion,ournationwidedatashowa
rise in the prevalence of chronic hyperten- h

sion(from1.01to1.76%)andsecondaryhy-pertension (from 0.07 to 0.24%), in deliveryhospitalizations in the United States from1995 through 2008, suggesting that the clini-calmanagementofthisproblemwill increas-ingly confront obstetricians and their col-leagues. Although primary and secondarychronic hypertension account for a substan-tial fraction of maternal morbidity and mor-tality, currentrecommendations for theclin-ical management of pregnant women withchronic hypertension are based on a fewsmall studies, with the benefits and risks ofthe available treatment strategies remaininguncertain.AsthedeliveringpopulationintheUnited States becomes older and moreobese,chronichypertensionratesarelikelytorise even further and this will therefore needto become a priority research area forobstetrics. f

REFERENCES1. Sibai BM. Chronic hypertension in pregnancy.

bstet Gynecol 2002;100:369-77.. American College of Obstetricians and Gyne-ologists. ACOG Committee on practice bulletins.COG practice bulletin: chronic hypertension inregnancy. Obstet Gynecol 2001;98(Suppl):77-85.. Ferrer RL, Sibai BM, Mulrow CD, Chiquette E,

Stevens KR, Cornell J. Management of mildchronic hypertension during pregnancy: a review.Obstet Gynecol 2000;96:849-60.4. Sibai BM, Lindheimer M, Hauth J, et al. Riskfactors for preeclampsia, abruption placentae,and adverse neonatal outcomes among womenwith chronic hypertension: National Institute ofChild Health and Human Development Networkof Maternal-Fetal Medicine Units. N Engl J Med1998;339:667-71.5. Rey E, Couturier A. The prognosis of preg-nancy in women with chronic hypertension. Am JObstet Gynecol 1994;171:410-6.6. Jain L. Effect of pregnancy-induced andchronic hypertension on pregnancy outcome. JPerinatol 1997;17:425-7.7. Ananth CV, Savitz DA, Bowes WA Jr. Hyper-tensive disorders of pregnancy and stillbirth inNorth Carolina, 1988 to 1991. Acta Obstet Gyne-col Scand 1995;74:788-93.8. Gilbert WM, Young AL, Danielsen B. Preg-nancy outcomes in women with chronic hyper-tension: a population-based study. J Reprod Med2007;52:1046-51.9. Sibai BM, Abdella TN, Anderson GD. Preg-ancy outcome in 211 patients with mild chronic
ypertension. Obstet Gynecol 1983;61:571-6. t
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0. Sibai BM, Anderson GD. Pregnancy out-ome of intensive therapy in severe hypertension

n first trimester. Obstet Gynecol 1986;67:17-22.1. Kuklina EV, Ayala C, Callaghan WM. Hyper-

ensive disorders and severe obstetric morbidity inhe United States. Obstet Gynecol 2009;13:1299-306.2. Bateman BT, Schumacher HC, Bushnell CD,t al. Intracerebral hemorrhage in pregnancy: fre-uency, risk factors, and outcome. Neurology006;67:424-9.3. Livingston JC, Sibai BM. Chronic hyperten-ion in pregnancy. Obstet Gynecol Clin North Am001;28:447-63.4. Martin JA, Hamilton BE, Sutton PD, et al.irths: final data for 2007. Natl Vital Stat Rep010;58:1-85.5. Kim SY, Dietz PM, England L, Morrow B, Cal-

aghan WM. Trends in pre-pregnancy obesity inine states, 1993-2003. Obesity (Silver Spring)007;15:986-93.6. Steiner C, Elixhauser A, Schnaier J. Theealthcare cost and utilization project: an over-iew. Eff Clin Pract 2002;5:143-51.7. Kuklina EV, Whiteman MK, Hillis SD, et al. Annhanced method for identifying obstetric deliver-

es: implications for estimating maternal morbidity.atern Child Health J 2008;12:469-77.8. Rockhill B, Newman B, Weinberg C. Use andisuse of population attributable fractions. Am Jublic Health 1998;88:15-9.9. Flenady V, Koopmans L, Middleton P, et al.ajor risk factors for stillbirth in high-income

ountries: a systematic review and meta-analysis.ancet 2011;377:1331-40.0. Allen VM, Joseph K, Murphy KE, Magee LA,hlsson A. The effect of hypertensive disorders inregnancy on small for gestational age and still-irth: a population based study. BMC Pregnancyhildbirth 2004;4:17.1. Canterino JC, Ananth CV, Smulian J, Harri-an JT, Vintzileos AM. Maternal age and risk of

etal death in singleton gestations: USA, 1995-000. J Matern Fetal Neonatal Med 2004;5:193-7.2. Zetterstrom K, Lindeberg SN, Haglund B,anson U. The association of maternal chronicypertension with perinatal death in male and fe-ale offspring: a record linkage study of 866,188omen. BJOG 2008;115:1436-42.3. von Dadelszen P, Ornstein MP, Bull SB, Lo-an AG, Koren G, Magee LA. Fall in mean arterialressure and fetal growth restriction in pregnancyypertension: a meta-analysis. Lancet 2000;55:87-92.4. Persson M, Norman M, Hanson U. Obstetricnd perinatal outcomes in type 1 diabetic preg-ancies: a large, population-based study. Diabe-
es Care 2009;32:2005-9.


APPENDIXList of International Classification of Diseases, Ninth Revision, Clinical Modification codes

Disease/comorbidities/outcome ICD-9-CM code................................................................................................................................................................................................................................................................................................................................................................................

Acute renal failure 669.3x, 584.x................................................................................................................................................................................................................................................................................................................................................................................

Cesarean delivery 74.x................................................................................................................................................................................................................................................................................................................................................................................

Chronic hypertension 642.0x-642.2x, 642.7x, 401.xx-405.xx................................................................................................................................................................................................................................................................................................................................................................................

Chronic renal disease 581.xx-583.xx, 585.xx, 587, 646.2x................................................................................................................................................................................................................................................................................................................................................................................

Coarctation of aorta 747.1x................................................................................................................................................................................................................................................................................................................................................................................

Collagen vascular disease 710.xx................................................................................................................................................................................................................................................................................................................................................................................

Cushing syndrome 255.0x................................................................................................................................................................................................................................................................................................................................................................................

Hyperplasia of renal artery 447.3x................................................................................................................................................................................................................................................................................................................................................................................

Hypoaldosteronism 255.1x................................................................................................................................................................................................................................................................................................................................................................................

Multiple births 651.xx................................................................................................................................................................................................................................................................................................................................................................................

Nongestational diabetes 249.xx-250.xx, 648.0x................................................................................................................................................................................................................................................................................................................................................................................

Pheochromocytoma 255.6x................................................................................................................................................................................................................................................................................................................................................................................

Poor fetal growth 656.5x................................................................................................................................................................................................................................................................................................................................................................................

Preeclampsia 642.4x-642.7x................................................................................................................................................................................................................................................................................................................................................................................

Previous cesarean delivery 654.2x................................................................................................................................................................................................................................................................................................................................................................................

Pulmonary edema 518.4................................................................................................................................................................................................................................................................................................................................................................................

Spontaneous delivery �37 wk gestation 644.2x................................................................................................................................................................................................................................................................................................................................................................................

Stillbirth 656.4x, V27.1, V27.3, V27.4, V27.6, V27.7................................................................................................................................................................................................................................................................................................................................................................................

Stroke/other cerebrovascular complications 325.xx, 346.6x, 348.1x, 348.3x, 348.4x, 348.5x, 430.xx- 434.xx, 436.xx-437.xx,671.5x, 674.0x, 997.0, 997.02.

................................................................................................................................................................................................................................................................................................................................................................................

Thyroid disorders 242.xx-244.xx, 648.1x................................................................................................................................................................................................................................................................................................................................................................................

Ventilation 96.7x................................................................................................................................................................................................................................................................................................................................................................................

ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification.


FEBRUARY 2012 American Journal of Obstetrics & Gynecology 134.e8

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