Objective
We sought to define the prevalence, trends, and outcomes of primary and secondary chronic hypertension in a population-based sample of deliveries.
Study Design
An estimated 56,494,634 deliveries were identified from the 1995 through 2008 Nationwide Inpatient Sample. The association of primary and secondary chronic hypertension with adverse fetal and maternal outcomes was evaluated using regression modeling and adjusted population-attributable fractions were calculated.
Results
During the study period, the prevalence of primary and secondary hypertension increased from 0.90% in 1995 through 1996 to 1.52% in 2007 through 2008 ( P for trend < .001) and from 0.07% to 0.24% ( P for trend < .001), respectively. The population-attributable fraction for chronic hypertension was considerable for many maternal adverse outcomes, including acute renal failure (21%), pulmonary edema (14%), preeclampsia (11%), and in-hospital mortality (10%).
Conclusion
Primary and secondary chronic hypertension were both strongly associated with adverse pregnancy outcomes and accounted for a substantial fraction of maternal morbidity. Prioritizing research efforts in this area is needed.
Chronic hypertension is a relatively common comorbidity in pregnancy and a well-established risk factor for a number of adverse perinatal outcomes, including preterm birth, perinatal death, and intrauterine growth restriction, as well as adverse maternal outcomes, including preeclampsia, stroke, acute renal failure, pulmonary edema, and maternal death. Although the majority of chronic hypertension among pregnant women is due to primary hypertension, about 10% of cases occur secondary to other medical conditions, such as diabetes mellitus, chronic renal disease, thyroid disease, and collagen vascular disease.
For Editors’ Commentary, see Table of Contents
There are few population-based studies examining the impact of chronic hypertension on obstetric outcomes in the United States ; this is particularly true for chronic hypertension that is secondary to or associated with other conditions. As the prevalence of advanced maternal age and obesity increase among childbearing women in the United States, both primary and secondary chronic hypertension are likely to become an increasingly common obstetric conditions.
The purpose of this study is 3-fold: (1) to examine nationwide trends in the prevalence of primary and secondary chronic hypertension during delivery hospitalizations in the United States; (2) to assess the effect of primary and secondary chronic hypertension on fetal and maternal obstetric complications; and (3) during the most recent years in the study period, to estimate the contribution of primary and secondary chronic hypertension to the burden of select fetal and maternal complications in the United States.
Materials and Methods
Hospital discharge data were obtained from the Nationwide Inpatient Sample (NIS), part of the Healthcare Cost and Utilization Project, a federal-state-industry partnership sponsored by the Agency for Healthcare Research and Quality. The NIS is a 20% stratified sample of all US community hospitals as defined by the American Hospital Association: nonfederal, short-term, general, and specialty hospitals whose facilities are open to the public. To create a sample that is maximally representative of all US community hospital admissions, hospital are selected for inclusion in the NIS based on 5 characteristics: rural/urban location, number of beds, region of the country, teaching status, and ownership. The NIS includes all discharges from the sampled hospitals and includes between 5-8 million discharges from an average of 1000 hospitals each year. Further information about the methodology used to create the dataset is available at http://www.hcup-us.ahrq.gov/nisoverview.jsp .
Our analysis included all delivery hospitalizations of women aged ≥15 years from 1995 through 2008; those who had abortions, ectopic pregnancies, or molar pregnancies were excluded from the analyses. Delivery hospitalizations were identified using a validated approach that selects admissions with relevant diagnosis-related groups and International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM ) diagnosis/procedure codes, as previously described. In addition, ICD-9-CM codes were used to classify hospitalizations with chronic hypertension, associated comorbidities, and maternal and fetal outcomes ( Appendix ).
| 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 |
Data management and statistical analyses were conducted using SAS (SAS Inc, Cary, NC) and SAS-callable SUDAAN software (version 9.2, RTI International, Research Triangle, NC) to account for the stratified sampling design used to collect the hospital discharge data. We used χ 2 tests with a significance level of .05 to compare the distribution of deliveries with and without chronic hypertension by sociodemographic and hospital characteristics and maternal comorbidities. For purposes of analysis, secondary hypertension was defined as chronic hypertension in association with conditions that can cause hypertension through either vascular or endocrinologic mechanisms including pregestational diabetes, chronic renal disease, collagen vascular disease (including systemic lupus erythematous, scleroderma, and other diffuse diseases of connective tissue), thyroid disorders, pheochromocytoma, hyperplasia of the renal artery, Cushing syndrome, hyperaldosteronism, and maternal coarctation of the aorta. Primary hypertension was defined as chronic hypertension without any of these associated comorbidities. To examine trends, the age-standardized prevalence of overall, primary, and secondary chronic hypertension, as well as chronic hypertension with selected individual comorbidities, were computed for 2-year intervals. Estimates were standardized by the age distribution of delivery hospitalizations for the last 2 years (2007 through 2008) and applying this distribution to the former 2-year intervals.
Given the increasing prevalence of chronic hypertension, we restricted our analyses of the effect of overall chronic hypertension, primary hypertension, and secondary hypertension on fetal and maternal outcomes to the last 2 years of the study period (2007 through 2008). Frequencies per 1000 deliveries were calculated for fetal outcomes (stillbirth, poor fetal growth, spontaneous delivery <37 weeks of gestation) and maternal outcomes (preeclampsia, stroke/cerebrovascular complications, acute renal failure, pulmonary edema, mechanical ventilation, cesarean delivery, length of hospital stay >6 days [corresponding to approximately the 98th percentile for length of stay], and in-hospital mortality), stratified by all-cause, primary, and secondary chronic hypertension status. Logistic regression was used to estimate odds ratios (ORs) and respective 95% confidence intervals of maternal and fetal delivery outcomes by maternal chronic hypertension status, while adjusting for multiple births, year of study, insurance status, region, and age; the models for cesarean delivery were additionally adjusted for previous cesarean delivery and the models for length of stay included adjustment for admission and disposition status. To estimate the burden of disease at the population level, population-attributable fractions for chronic hypertension (overall), primary hypertension, and secondary hypertension for each of the fetal and maternal outcomes of interest were calculated using adjusted OR as estimates of relative risk, as described elsewhere. The population-attributable fraction estimates the proportion of disease that would be eliminated if the exposure, in this case chronic hypertension, could be eliminated.
A similar analysis was conducted examining the association of chronic hypertension with the comorbidities most commonly associated with chronic hypertension–pregestational diabetes, chronic renal disease, collagen vascular disease, and thyroid disorders–and selected fetal/maternal outcomes. Because of the relatively small numbers of patients with chronic hypertension and the comorbidities considered, the NIS for the entire study period (1995 through 2008) was used for this analysis to ensure adequate power to make reliable estimates of risk.
Results
From 1995 through 2008, an estimated 56,494,634 delivery hospitalizations were identified, of which 731,694 were classified as deliveries with chronic hypertension. Of the patients with chronic hypertension, 649,899 (88.8%) had primary hypertension and 81,795 (11.2%) had secondary hypertension; in the final 2 years of the study period (2007 through 2008), of the 153,570 patients with chronic hypertension, 132,808 (86.5%) had primary hypertension and 20,762 (13.5%) had secondary hypertension. Compared to women with delivery hospitalizations without chronic hypertension, those with chronic hypertension were older, and had higher rates of multiple birth, previous cesarean delivery, pregestational diabetes, chronic renal disease, collagen vascular disease, hyperaldosteronism, Cushing disease, thyroid disease, and maternal coarctation of the aorta (all P < .001) ( Table 1 ). The most common comorbidities associated with chronic hypertension included pregestational diabetes (present in 6.6% of chronic hypertension admissions), thyroid disorders (present in 4.1%), chronic renal disease (present in 0.9%), and collagen vascular disease (present in 0.6%).
| Characteristic | With chronic hypertension (N = 731,694), n (%) | Without chronic hypertension (N = 55,762,940), n (%) | P a 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 | |||
| Public b | 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) |
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