Comparison of risk factors and outcomes of gestational hypertension and pre-eclampsia

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Abstract

Background

It remains an enigma whether gestational hypertension (GH) and pre-eclampsia (PE) are distinct entities or different spectrum of the same disease. We aimed to compare the risk factors and outcomes between GH and PE.

Method

A total of 7,633 pregnant women recruited between 12 and 20 weeks of gestation in the Ottawa and Kingston Birth Cohort from 2002 to 2009 were included in the analysis. Cox proportional hazards model was used to identify and compare the risk factors for GH and PE by treating gestational age at delivery as the survival time. Logistic regression model was used to compare outcome. Subgroup analysis was performed for early- and late-onset PE.

Results

GH and PE shared most risk factors including overweight and obesity, nulliparity, PE history, type 1 and 2 diabetes, and twin birth. Effect size of PE history (RR = 14.1 for GH vs. RR = 6.4 for PE) and twin birth (RR = 4.8 for GH vs. RR = 10.3 for PE) showed substantial difference. Risk factors modified gestational age at delivery in patients with GH and PE in similar pattern. Subgroup analysis showed that early- and late-onset PE shared some risk factors with different effect sizes, whereas folic acid supplementation showed protective effect for early-onset PE only. PE was strongly associated with several adverse outcomes including cesarean section, placental abruption, small for gestational age, preterm birth, and 5 min Apgar score < 7, whereas GH was associated with increased risk of preterm birth only.

Conclusions

GH and PE shared common risk factors. Differences in effect sizes of risk factors and outcomes indicate that the conditions may have different pathophysiology and mechanism.

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Most cited references 37

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Circulating angiogenic factors and the risk of preeclampsia.

Richard J. Levine, Sharon E. Maynard, Cong Qian … (2004)

The cause of preeclampsia remains unclear. Limited data suggest that excess circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), may have a pathogenic role. We performed a nested case-control study within the Calcium for Preeclampsia Prevention trial, which involved healthy nulliparous women. Each woman with preeclampsia was matched to one normotensive control. A total of 120 pairs of women were randomly chosen. Serum concentrations of angiogenic factors (total sFlt-1, free PlGF, and free VEGF) were measured throughout pregnancy; there were a total of 655 serum specimens. The data were analyzed cross-sectionally within intervals of gestational age and according to the time before the onset of preeclampsia. During the last two months of pregnancy in the normotensive controls, the level of sFlt-1 increased and the level of PlGF decreased. These changes occurred earlier and were more pronounced in the women in whom preeclampsia later developed. The sFlt-1 level increased beginning approximately five weeks before the onset of preeclampsia. At the onset of clinical disease, the mean serum level in the women with preeclampsia was 4382 pg per milliliter, as compared with 1643 pg per milliliter in controls with fetuses of similar gestational age (P<0.001). The PlGF levels were significantly lower in the women who later had preeclampsia than in the controls beginning at 13 to 16 weeks of gestation (mean, 90 pg per milliliter vs. 142 pg per milliliter, P=0.01), with the greatest difference occurring during the weeks before the onset of preeclampsia, coincident with the increase in the sFlt-1 level. Alterations in the levels of sFlt-1 and free PlGF were greater in women with an earlier onset of preeclampsia and in women in whom preeclampsia was associated with a small-for-gestational-age infant. Increased levels of sFlt-1 and reduced levels of PlGF predict the subsequent development of preeclampsia. Copyright 2004 Massachusetts Medical Society

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A new and improved population-based Canadian reference for birth weight for gestational age.

M Kramer, R W Platt, S Wen … (2001)

Existing fetal growth references all suffer from 1 or more major methodologic problems, including errors in reported gestational age, biologically implausible birth weight for gestational age, insufficient sample sizes at low gestational age, single-hospital or other non-population-based samples, and inadequate statistical modeling techniques. We used the newly developed Canadian national linked file of singleton births and infant deaths for births between 1994 and 1996, for which gestational age is largely based on early ultrasound estimates. Assuming a normal distribution for birth weight at each gestational age, we used the expectation-maximization algorithm to exclude infants with gestational ages that were more consistent with 40-week births than with the observed gestational age. Distributions of birth weight at the corrected gestational ages were then statistically smoothed. The resulting male and female curves provide smooth and biologically plausible means, standard deviations, and percentile cutoffs for defining small- and large-for-gestational-age births. Large-for-gestational age cutoffs (90th percentile) at low gestational ages are considerably lower than those of existing references, whereas small-for-gestational-age cutoffs (10th percentile) postterm are higher. For example, compared with the current World Health Organization reference from California (Williams et al, 1982) and a recently proposed US national reference (Alexander et al, 1996), the 90th percentiles for singleton males at 30 weeks are 1837 versus 2159 and 2710 g. The corresponding 10th percentiles at 42 weeks are 3233 versus 3086 and 2998 g. This new sex-specific, population-based reference should improve clinical assessment of growth in individual newborns, population-based surveillance of geographic and temporal trends in birth weight for gestational age, and evaluation of clinical or public health interventions to enhance fetal growth. fetal growth, birth weight, gestational age, preterm birth, postterm birth.

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Early and late preeclampsia: two different maternal hemodynamic states in the latent phase of the disease.

Barbara Vasapollo, Herbert Valensise, G. Gagliardi … (2008)

Because early and late preeclampsia (PE) are thought to be different disease entities, we compared maternal cardiac function at 24 weeks gestation in a group of normotensive asymptomatic patients with subsequent development of early ( or=34 weeks gestation) PE (blood pressure >140/90+proteinuria >300 mg/dL) to detect possible early differences in the hemodynamic state. A group of 1345 nulliparous normotensive asymptomatic women underwent at 24 weeks gestation uterine artery Doppler evaluation and maternal echocardiography calculating total vascular resistance. In the subsequent follow-up 107 patients showed PE: 32 patients had late and 75 had early PE. Five of 32 patients with late PE and 45 of 75 patients with early PE had bilateral notching of the uterine artery at 24 weeks (15.6% versus 60.0%; P<0.05). Total vascular resistance was 1605+/-248 versus 739+/-244 dyn . s . cm(-5), and cardiac output was 4.49+/-1.09 versus 8.96+/-1.83 L in early versus late PE (P<0.001). Prepregnancy body mass index was higher in late versus early PE (28+/-6 versus 24+/-2 kg/m(2); P<0.001). Early and late PE appear to develop from different hemodynamic states. Late PE appears to be more frequent in patients with high body mass index and low total vascular resistance; earlier forms of PE appear to be more frequent in patients with lower BMI and with bilateral notching of the uterine artery. These findings support the hypothesis of different hemodynamics and origins for early PE (placental mediated, linked to defective trophoblast invasion with high percentage of altered uterine artery Doppler) and late PE (linked to constitutional factors such as high body mass index).

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Author and article information

Contributors

Sari Helena Räisänen: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 24 April 2017

Publication date Collection: 2017

Volume: 12

Issue: 4

Electronic Location Identifier: e0175914

Affiliations

[1 ]Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China

[2 ]Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China

[3 ]OMNI Research Group, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada

[4 ]Ottawa Hospital Research Institute, Clinical Epidemiology Program, Ottawa, Ontario, Canada

[5 ]Department of Obstetrics and Gynecology, Queen’s University, Kingston, Ontario, Canada

[6 ]School of Epidemiology, Public Health, and Preventive Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada

[7 ]Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada

Helsingin Yliopisto, FINLAND

Author notes

Competing Interests: The authors have declared that no competing interests exist.

Conceptualization: SWW.
Data curation: MS.
Formal analysis: MS.
Funding acquisition: SWW.
Investigation: GNS MR RRW MCW SWW.
Methodology: SWW.
Project administration: RRW.
Resources: SWW MCW.
Software: MS.
Supervision: SWW.
Validation: SWW MCW.
Visualization: MS.
Writing – original draft: MS.
Writing – review & editing: GNS MCW SWW.

* E-mail: swwen@ 123456ohri.ca

Author information

Shi Wu Wen http://orcid.org/0000-0002-2681-741X

Article

Publisher ID: PONE-D-16-46897

DOI: 10.1371/journal.pone.0175914

PMC ID: 5402970

PubMed ID: 28437461

SO-VID: 5ff14ad8-146d-45e3-ab5a-9432d9eeaeae

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 26 November 2016

Date accepted : 2 April 2017

Page count

Figures: 1, Tables: 4, Pages: 13

Funding

Funded by: funder-id http://dx.doi.org/10.13039/501100000024, Canadian Institutes of Health Research;

Award ID: MOP53188

Award Recipient :

ORCID: http://orcid.org/0000-0002-2681-741X

Shi Wu Wen

Funded by: funder-id http://dx.doi.org/10.13039/501100000024, Canadian Institutes of Health Research;

Award ID: MOP 82802

Award Recipient :

ORCID: http://orcid.org/0000-0002-2681-741X

Shi Wu Wen

Funded by: funder-id http://dx.doi.org/10.13039/501100000024, Canadian Institutes of Health Research;

Award ID: MCT-98030

Award Recipient :

ORCID: http://orcid.org/0000-0002-2681-741X

Shi Wu Wen

This work was supported by the Canadian Institutes of Health Research, Grant Nos.: MOP53188, MOP 82802, MCT-98030 to SWW. URL: http://www.cihr-irsc.gc.ca/e/193.html.

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Comparison of risk factors and outcomes of gestational hypertension and pre-eclampsia

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Abstract

Background

Method

Results

Conclusions

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PLOS Climate

Most cited references 37

Circulating angiogenic factors and the risk of preeclampsia.

A new and improved population-based Canadian reference for birth weight for gestational age.

Early and late preeclampsia: two different maternal hemodynamic states in the latent phase of the disease.

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