Skip to main content
  • American Heart Association
  • Science Volunteer
  • Warning Signs
  • Advanced Search
  • Donate

  • Home
  • About this Journal
    • General Statistics
    • Editorial Board
    • Editors
    • Information for Advertisers
    • Author Reprints
    • Commercial Reprints
    • Customer Service and Ordering Information
  • All Issues
  • Subjects
    • All Subjects
    • Arrhythmia and Electrophysiology
    • Basic, Translational, and Clinical Research
    • Critical Care and Resuscitation
    • Epidemiology, Lifestyle, and Prevention
    • Genetics
    • Heart Failure and Cardiac Disease
    • Hypertension
    • Imaging and Diagnostic Testing
    • Intervention, Surgery, Transplantation
    • Quality and Outcomes
    • Stroke
    • Vascular Disease
  • Browse Features
    • AHA Guidelines and Statements
    • Acknowledgment of Reviewers
    • Clinical Implications
    • Clinical-Pathological Conferences
    • Controversies in Hypertension
    • Editors' Picks
    • Guidelines Debate
    • Meeting Abstracts
    • Recent Advances in Hypertension
    • SPRINT Trial: the Conversation Continues
  • Resources
    • Instructions to Reviewers
    • Instructions for Authors
    • →Article Types
    • → Submission Guidelines
      • Research Guidelines
        • Minimum Information About Microarray Data Experiments (MIAME)
      • Abstract
      • Acknowledgments
      • Clinical Implications (Only by invitation)
      • Conflict(s) of Interest/Disclosure(s) Statement
      • Figure Legends
      • Figures
      • Novelty and Significance: 1) What Is New, 2) What Is Relevant?
      • References
      • Sources of Funding
      • Tables
      • Text
      • Title Page
      • Online/Data Supplement
    • →Tips for Easier Manuscript Submission
    • → General Instructions for Revised Manuscripts
      • Change of Authorship Form
    • → Costs to Authors
    • → Open Access, Repositories, & Author Rights Q&A
    • Permissions to Reprint Figures and Tables
    • Journal Policies
    • Scientific Councils
    • AHA Journals RSS Feeds
    • International Users
    • AHA Newsroom
  • AHA Journals
    • AHA Journals Home
    • Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB)
    • Circulation
    • → Circ: Arrhythmia and Electrophysiology
    • → Circ: Genomic and Precision Medicine
    • → Circ: Cardiovascular Imaging
    • → Circ: Cardiovascular Interventions
    • → Circ: Cardiovascular Quality & Outcomes
    • → Circ: Heart Failure
    • Circulation Research
    • Hypertension
    • Stroke
    • Journal of the American Heart Association
  • Facebook
  • Twitter

  • My alerts
  • Sign In
  • Join

  • Advanced search

Header Publisher Menu

  • American Heart Association
  • Science Volunteer
  • Warning Signs
  • Advanced Search
  • Donate

Hypertension

  • My alerts
  • Sign In
  • Join

  • Facebook
  • Twitter
  • Home
  • About this Journal
    • General Statistics
    • Editorial Board
    • Editors
    • Information for Advertisers
    • Author Reprints
    • Commercial Reprints
    • Customer Service and Ordering Information
  • All Issues
  • Subjects
    • All Subjects
    • Arrhythmia and Electrophysiology
    • Basic, Translational, and Clinical Research
    • Critical Care and Resuscitation
    • Epidemiology, Lifestyle, and Prevention
    • Genetics
    • Heart Failure and Cardiac Disease
    • Hypertension
    • Imaging and Diagnostic Testing
    • Intervention, Surgery, Transplantation
    • Quality and Outcomes
    • Stroke
    • Vascular Disease
  • Browse Features
    • AHA Guidelines and Statements
    • Acknowledgment of Reviewers
    • Clinical Implications
    • Clinical-Pathological Conferences
    • Controversies in Hypertension
    • Editors' Picks
    • Guidelines Debate
    • Meeting Abstracts
    • Recent Advances in Hypertension
    • SPRINT Trial: the Conversation Continues
  • Resources
    • Instructions to Reviewers
    • Instructions for Authors
    • →Article Types
    • → Submission Guidelines
    • →Tips for Easier Manuscript Submission
    • → General Instructions for Revised Manuscripts
    • → Costs to Authors
    • → Open Access, Repositories, & Author Rights Q&A
    • Permissions to Reprint Figures and Tables
    • Journal Policies
    • Scientific Councils
    • AHA Journals RSS Feeds
    • International Users
    • AHA Newsroom
  • AHA Journals
    • AHA Journals Home
    • Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB)
    • Circulation
    • → Circ: Arrhythmia and Electrophysiology
    • → Circ: Genomic and Precision Medicine
    • → Circ: Cardiovascular Imaging
    • → Circ: Cardiovascular Interventions
    • → Circ: Cardiovascular Quality & Outcomes
    • → Circ: Heart Failure
    • Circulation Research
    • Hypertension
    • Stroke
    • Journal of the American Heart Association
Original Article

Serum Leptin Measured in Early Pregnancy Is Higher in Women With Preeclampsia Compared With Normotensive Pregnant WomenNovelty and Significance

Brandie D. Taylor, Roberta B. Ness, Jørn Olsen, David M. Hougaard, Kristin Skogstrand, James M. Roberts, Catherine L. Haggerty
Download PDF
https://doi.org/10.1161/HYPERTENSIONAHA.114.03979
Hypertension. 2015;65:594-599
Originally published December 15, 2014
Brandie D. Taylor
From the Department of Epidemiology, Graduate School of Public Health (B.D.T., J.M.R., C.L.H.), and Department of Obstetrics, Gynecology, and Reproductive Sciences (J.M.R.), University of Pittsburgh, PA; Department of Epidemiology and Biostatistics, Texas A&M Health Science Center, College Station (B.D.T.); University of Texas School of Public Health, Houston (R.B.N.); Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark (J.O.); Danish Centre for Neonatal Screening, Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark (D.M.H., K.S.); Magee-Womens Research Institute, University of Pittsburgh Medical Center, PA (J.M.R., C.L.H.); and Department of Clinical and Translational Research, University of Pittsburgh, PA (J.M.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roberta B. Ness
From the Department of Epidemiology, Graduate School of Public Health (B.D.T., J.M.R., C.L.H.), and Department of Obstetrics, Gynecology, and Reproductive Sciences (J.M.R.), University of Pittsburgh, PA; Department of Epidemiology and Biostatistics, Texas A&M Health Science Center, College Station (B.D.T.); University of Texas School of Public Health, Houston (R.B.N.); Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark (J.O.); Danish Centre for Neonatal Screening, Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark (D.M.H., K.S.); Magee-Womens Research Institute, University of Pittsburgh Medical Center, PA (J.M.R., C.L.H.); and Department of Clinical and Translational Research, University of Pittsburgh, PA (J.M.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jørn Olsen
From the Department of Epidemiology, Graduate School of Public Health (B.D.T., J.M.R., C.L.H.), and Department of Obstetrics, Gynecology, and Reproductive Sciences (J.M.R.), University of Pittsburgh, PA; Department of Epidemiology and Biostatistics, Texas A&M Health Science Center, College Station (B.D.T.); University of Texas School of Public Health, Houston (R.B.N.); Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark (J.O.); Danish Centre for Neonatal Screening, Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark (D.M.H., K.S.); Magee-Womens Research Institute, University of Pittsburgh Medical Center, PA (J.M.R., C.L.H.); and Department of Clinical and Translational Research, University of Pittsburgh, PA (J.M.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David M. Hougaard
From the Department of Epidemiology, Graduate School of Public Health (B.D.T., J.M.R., C.L.H.), and Department of Obstetrics, Gynecology, and Reproductive Sciences (J.M.R.), University of Pittsburgh, PA; Department of Epidemiology and Biostatistics, Texas A&M Health Science Center, College Station (B.D.T.); University of Texas School of Public Health, Houston (R.B.N.); Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark (J.O.); Danish Centre for Neonatal Screening, Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark (D.M.H., K.S.); Magee-Womens Research Institute, University of Pittsburgh Medical Center, PA (J.M.R., C.L.H.); and Department of Clinical and Translational Research, University of Pittsburgh, PA (J.M.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kristin Skogstrand
From the Department of Epidemiology, Graduate School of Public Health (B.D.T., J.M.R., C.L.H.), and Department of Obstetrics, Gynecology, and Reproductive Sciences (J.M.R.), University of Pittsburgh, PA; Department of Epidemiology and Biostatistics, Texas A&M Health Science Center, College Station (B.D.T.); University of Texas School of Public Health, Houston (R.B.N.); Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark (J.O.); Danish Centre for Neonatal Screening, Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark (D.M.H., K.S.); Magee-Womens Research Institute, University of Pittsburgh Medical Center, PA (J.M.R., C.L.H.); and Department of Clinical and Translational Research, University of Pittsburgh, PA (J.M.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James M. Roberts
From the Department of Epidemiology, Graduate School of Public Health (B.D.T., J.M.R., C.L.H.), and Department of Obstetrics, Gynecology, and Reproductive Sciences (J.M.R.), University of Pittsburgh, PA; Department of Epidemiology and Biostatistics, Texas A&M Health Science Center, College Station (B.D.T.); University of Texas School of Public Health, Houston (R.B.N.); Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark (J.O.); Danish Centre for Neonatal Screening, Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark (D.M.H., K.S.); Magee-Womens Research Institute, University of Pittsburgh Medical Center, PA (J.M.R., C.L.H.); and Department of Clinical and Translational Research, University of Pittsburgh, PA (J.M.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Catherine L. Haggerty
From the Department of Epidemiology, Graduate School of Public Health (B.D.T., J.M.R., C.L.H.), and Department of Obstetrics, Gynecology, and Reproductive Sciences (J.M.R.), University of Pittsburgh, PA; Department of Epidemiology and Biostatistics, Texas A&M Health Science Center, College Station (B.D.T.); University of Texas School of Public Health, Houston (R.B.N.); Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark (J.O.); Danish Centre for Neonatal Screening, Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark (D.M.H., K.S.); Magee-Womens Research Institute, University of Pittsburgh Medical Center, PA (J.M.R., C.L.H.); and Department of Clinical and Translational Research, University of Pittsburgh, PA (J.M.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Tables
  • Info & Metrics
  • eLetters

Jump to

  • Article
    • Abstract
    • Introduction
    • Methods
    • Results
    • Discussion
    • Sources of Funding
    • Disclosures
    • References
  • Figures & Tables
  • Info & Metrics
  • eLetters
Loading

Abstract

Leptin, an adipocyte-derived hormone, plays an important role in reproduction and angiogenesis. Studies examining leptin in preeclampsia are inconsistent, possibly because of small sample sizes and variability in sampling and outcome. We conducted a nested case–control study to examine associations between serum leptin (measured: 9–26 weeks gestation) and preeclampsia among 430 primiparous preeclamptic women and 316 primiparous normotensive controls from the Danish National Birth Cohort. Median (interquartile range) leptin concentrations were calculated. Associations between leptin and preeclampsia (blood pressure ≥140/90 mm Hg), term preeclampsia (preeclampsia and delivery ≥37 weeks gestation), or preterm preeclampsia (preeclampsia and delivery <37 weeks gestation) were examined using generalized linear models adjusting for body mass index, gestational age at blood draw, maternal age, smoking, and socio-occupational status. As leptin is increased in obese women and the risk of preeclampsia increases with body mass index, we used the Sobel test to examine whether leptin is a mediator of this relationship. After adjustments, leptin concentrations were significantly higher in women with preeclampsia (30.5 [24.6]; P=0.0117) and term preeclampsia (30.4 [24.9]; P=0.0228) compared with controls (20.9 [28.3]). There was no significant difference between preterm preeclampsia (30.6 [23.4]; P=0.2210) and controls. Leptin is a possible mediator of the association between body mass index and preeclampsia (P=0.0276). Leptin concentrations are higher in women with preeclampsia compared with normotensive controls and may mediate some of the relationship between body mass index and preeclampsia.

  • body mass index
  • hypertension
  • leptin
  • preeclampsia
  • pregnancy

Introduction

Leptin is a hormone that plays an important role in several physiological processes, including the regulation of endocrine function, immune function, inflammation, reproduction, and angiogenesis.1 The main source of leptin is adipose tissue, but during pregnancy, leptin is also produced by the placenta.2 In normal pregnancy, placental leptin expression is increased compared with nonpregnant women and suggested to support implantation, human chorionic gonadotrophin production, placental growth, amino acid uptake, and mitogenesis.3 Thus, a dysregulation in leptin levels may indicate or lead to maternal disease. For example, placental leptin expression4,5 and circulating leptin levels4,6–9 are exaggerated in preeclampsia, a systemic maternal syndrome characterized by the new onset of hypertension and proteinuria after 20 weeks of gestation.10 Because the only treatment for preeclampsia is delivery of the placenta,10 which can be preterm, there is a need to identify biomarkers for early prediction or to identify women with severe subtypes who require different clinical management.11 Thus, leptin could be a potential biomarker for preeclampsia.

Elevated placental leptin expression in preeclampsia is consistent with the accepted model that placental dysfunction leads to an increase in placental-associated factors released into the maternal circulation, resulting in maternal systemic disease.12 One hypothesis is that leptin is increased as a result of placental stress to increase nutrient delivery to the fetus.5 Alternatively, excessive maternal inflammation coupled with other placental factors may mediate excessive leptin expression in preeclamptic women.13 In both scenarios, increased placental leptin could be a valuable proxy for disease. In addition, there is evidence that leptin may play a direct role in preeclampsia pathogenesis. Increased leptin leads to hypertension in mouse models14 and has been shown to increase blood pressure through sympathetic activation and nitric oxide synthesis.15 Furthermore, leptin may have proinflammatory properties,16 and inflammation is associated with preeclampsia.17

Although epidemiological studies have shown significant associations between leptin and preeclampsia, some studies have found no association after adjustment for maternal characteristics, including body mass index (BMI).18–20 Indeed serum leptin is increased with obesity,6 and increasing BMI has been shown to be linked with preeclampsia.21,22 However, it is possible that leptin partly mediates this association. This may occur as a result of an increase in placental leptin resistance and a dysregulation of leptin function, which is observed in obese women.23 We aimed to examine the association between serum leptin in early pregnancy (9–26 weeks gestation) and preeclampsia defined by severity among 430 preeclamptic women and 316 normotensive controls from the Danish National Birth Cohort (DNBC). In addition, we explored whether leptin mediated the association between maternal BMI and preeclampsia.

Methods

Study Population

This study was part of a previously completed nested case control study of 562 primiparous women with preeclampsia, singleton pregnancies, and no gestational diabetes mellitus and 377 primiparous normotensive controls with singleton pregnancies and no gestational diabetes mellitus selected from the DNBC.24 Our subset has similar characteristics compared with primiparous/singleton women in the DNBC. For example, in both groups, most women had a maternal age between 26 and 30 (52.9% versus 52.2%) and a high socio-occupational status (67.5% versus 64.9%). There were slight differences in BMI (normal, 70.6% versus 62.5%) and smoking (25.3% versus 18.8%) due mainly to the larger percentage of preeclamptic women in our cohort who are more likely to have increased BMI and less likely to smoke.10 The DNBC is a longitudinal population-based cohort of 101 033 pregnancies and their offspring. Details on the methods of recruitment, retention, and data collection have been published elsewhere.25 Briefly, between 1996 and 2003, women who were receiving prenatal care were recruited at first prenatal visits by their general practitioners. At the first study visit, pregnancy was confirmed and a blood sample was obtained. Telephone interviews were administered at recruitment (median 16 weeks, range 6–40 weeks), at 30 weeks gestation, and twice after delivery. For this study, cohort members were merged with National Birth Register and National Hospital Discharge Register via a unique personal code given to citizens of Denmark. Gestational age was determined by last menstrual period reported but corrected with an early ultrasound if the subject reported use of contraception 4 months before conception, had irregular periods, or had an abnormal last menstrual cycle. The DNBC was approved by the Danish Ethics Central Committee.

For this substudy, leptin results were available for 512 cases and 339 controls. Women with a history of hypertension (n=75) and those with samples obtained in the third trimester (n=30) were excluded from the analyses, yielding 430 cases and 316 controls with markers assessed at recruitment dates ranging from 9 to 26 weeks of gestation. The majority of samples in our study were collected in the second trimester (n=675; median 17 weeks). An additional 71 samples were from women recruited in the first trimester (median 12 weeks). The main analyses were conducted pooling these samples together because inclusion of the relatively small number of first trimester samples was not expected to significantly influence the results. Furthermore, median leptin levels were similar in the first and second trimester samples (29.6 [interquartile range, 27.25] versus 24.9 [interquartile range, 26.3]; P=0.5432). This study was approved by the University of Pittsburgh Institutional Review Board and the Danish Data Protection Agency.

Preeclampsia Definition

Women with preeclampsia were identified by a positive report of preeclampsia at the postnatal interview and confirmed by an International Classification of Diseases (ICD) code and discharge diagnoses in the National Hospital Discharge Registry of 637.03, 637.04, 637.09, 637.19 (ICD-8) or D014 to D015 (ICD-10). Preeclampsia was determined if a women had either systolic or diastolic blood pressure ≥140/90 mm Hg measured twice with an interval of 6 hours and the presence of proteinuria (≥0.3 g/24 hours or 1+ urine dipstick measured twice with an interval of 4 hours). A chart abstraction study within the DNBC shows that compared with a chart review using American College of Obstetrics and Gynecology (ACOG) criteria, the Danish National Discharge Registry yields a highly specific diagnosis of preeclampsia (99%).26 Preeclampsia is a heterogeneous syndrome.27 For example, early and late onset preeclampsia are suggested subtypes with different pathophysiological pathways and clinical presentation.27 In this analysis, we further classified preeclampsia resulting in either a term birth (≥37 weeks gestation) or a preterm birth (<37 weeks of gestation) as separate outcomes. Preeclampsia with preterm birth was used as a proxy for severity and early onset.

Leptin Measurement

Whole blood samples obtained at the first study visit were mailed to the Statens Serum Institute in Copenhagen and were separated and stored at −80°C. The average time from collection to processing was 28 hours. Leptin was measured in duplicate with an in-house assay28,29 using the multiplex flow cytometric assay system Luminex MultiAnalyte Profiling Technology (LabMap; Luminex Corporation, Austin, TX). The calibration curve was calculated by the Bio-Plex 3.0 software (BioRad). A 5-parameter logistic regression equation was used to determine leptin concentrations. The working range for leptin was assessed from the precision profile and defined as the concentration range where the coefficient of variation was <20%.29

Maternal Characteristics

During the first study interview, women reported the following: gravidity/parity, occupation, cigarette use during pregnancy, prior medical conditions, prior spontaneous abortions, and prepregnancy weight and height. Maternal age was self-reported at delivery and grouped as ≥25, 26 to 30, and 31+. Socio-occupational status was based on a women’s job classification or education. High status was assigned to women in management or jobs that required >4 years of post-high school education. Mid status was assigned to those with office, service, or skilled manual workers or women in the military. Low status included unskilled or unemployed women. Pre-pregnancy BMI was determined using reported height and weight at the first study interview and was categorized as underweight or normal (<25), overweight (≥25 and <30), or obese (≥30).

Statistical Analyses

Baseline variables, including gestational age at blood draw, maternal age, BMI, smoking, and sociooccupational status, were compared between all preeclamptic cases and normotensive controls. In addition, we compared rates of preterm birth between cases and controls. Logistic regression was used to examine associations between variables and preeclampsia. A P value <0.05 was used to determine statistical significance. The median and interquartile range for leptin was calculated for preeclampsia, preeclampsia defined by gestational age of delivery, and normotensive controls. Distributions were compared by Wilcoxon rank-sum test. To determine whether leptin concentrations and preeclampsia were significantly associated, P values were calculated using generalized linear models. As leptin is not normally distributed, the logarithm of leptin with base 2 was used (this represents a doubling of intensity). Additionally, leptin was dichotomized (≥median) and logistic regression was used to calculate odds ratio (ORs; as an estimate for relative risk), and 95% confidence interval (CI). Dichotomizing by the median is 1 method to analyze biomarkers with limits of detection.30 However, we chose to also examine the data in the continuous models to determine whether there was consistency among both modeling approaches. Maternal age, gestational age at blood draw, BMI, smoking, and socio-occupational status were included in all regression models. Finally, we explored whether leptin mediated the relationship between BMI and preeclampsia using a modified version of the Sobel test for binary outcomes.31 Statistical significance was determined as a P value <0.05. Although adequately powered for our main analyses, a post hoc power analysis reveals that our power was reduced (60%) to detect significant differences in leptin levels between preterm preeclampsia and normotensive controls (based on calculated medians). All analyses were conducted using SAS V9.2 (Cary, NC).

Results

Table 1 compares characteristics between all women with preeclampsia and normotensive controls. The majority of women in our cohort were between the ages of 26 and 30, had a BMI <25, did not smoke during pregnancy, had a high socio-occupational status, and delivered a term infant. When we compared baseline variables between cases and controls, we found that overweight women (OR, 1.9; 95% CI, 1.3–2.8; P=0.0006), obese women (OR, 4.1; 95% CI, 2.4–7.4; P<0.0001), and women with low socio-occupational status (OR, 2.8; 95% CI, 1.1–7.1; P=0.0263) had a higher odds of preeclampsia. Women who smoked at the time of enrollment were significantly less likely to have preeclampsia (OR, 0.6; 95% CI, 0.3–0.9; P=0.0158). In addition, preeclamptic women were significantly more likely to have a preterm infant <37 weeks gestation (OR, 6.8; 95% CI, 3.7–12.7; P<0.0001) and <34 weeks gestation (OR, 4.2; 95% CI, 1.5–10.9; P=0.0038).

View this table:
  • View inline
  • View popup
Table 1.

Comparison of Baseline and Pregnancy Outcome Variables Between Preeclamptic Women and Normotensive Controls

Compared with normotensive controls (n=316; median 20.9 [interquartile range, 28.3]), leptin concentration levels were higher in women with preeclampsia (n=430; 30.5 [24.6]; P<0.0001). Results were similar for women with preterm preeclampsia (n=91; 30.6 [23.4]; P=0.0192) and term preeclampsia (n=339; 30.4 [24.9]; P<0.0001). After adjustments for maternal age, gestational age at blood draw, BMI, smoking, and socio-occupational status, there was a significant association between leptin and preeclampsia (P=0.0117) where each unit increase in leptin increased the log odds of having preeclampsia versus being normotensive (Table 2). Results were similar in women with term preeclampsia (P=0.0228). Leptin was not significantly associated with preterm preeclampsia (P=0.2210). Median leptin concentrations in early pregnancy were higher among women with preeclampsia, resulting in a preterm birth <34 weeks (41.0 [23.1]) as compared with controls, although the sample size of these cases was limited (n=27) and multivariate models did not show a significant association (P=0.7646). We conducted our analysis in second trimester samples only (n=675) and found that leptin remained significantly associated with preeclampsia (P=0.0061). Similarly, if we examine a smaller gestational age range between 15 and 18 weeks (n=308), before the diagnosis of preeclampsia and when the majority of samples were collected, leptin remains significantly associated with preeclampsia (P=0.0332).

View this table:
  • View inline
  • View popup
Table 2.

Associations Between Leptin Concentrations and Preeclampsia Subtypes

Dichotomized models examining associations between elevated leptin (≥median) and preeclampsia yielded similar results (Table 3). Elevated leptin increased the odds of preeclampsia (OR, 1.4; 95% CI, 1.0–2.0). Results were similar for preterm (OR, 1.8; 95% CI, 1.1–3.0) and term preeclampsia (OR, 1.4; 95% CI, 1.0–2.0).

View this table:
  • View inline
  • View popup
Table 3.

Associations Between Elevated Leptin Dichotomized Above the Median and Preeclampsia Subtypes

In our cohort, lean women (18.9 [23.1]) had lower median leptin levels than overweight or obese women (41 [3.7]). Furthermore, increasing BMI was significantly associated with increased leptin levels independent of gestational age at blood draw, maternal age, smoking, or socio-occupational status (P<0.0001). We evaluated whether leptin may mediate the relationship between BMI and preeclampsia using the Sobel test. Leptin was a potential mediator of BMI and preeclampsia (P=0.0276) and accounted for 19.6% of the total effect.

Discussion

Our results demonstrate that serum leptin concentrations measured in early pregnancy are significantly higher in women with preeclampsia compared with normotensive controls after adjusting for known confounding factors, including BMI. Furthermore, examining leptin in a smaller gestational age range before 20 weeks when preeclampsia would be diagnosed shows similar results. Therefore, leptin may be elevated in women who will subsequently develop preeclampsia. Our results are consistent with several small studies conducted in the third trimester that have found elevated maternal leptin in preeclamptic women compared with healthy pregnant controls.4,6–9 In contrast, a longitudinal examination of leptin in 71 preeclamptic women and 71 age-, parity-, and BMI-matched controls reported lower leptin levels at 18 weeks of gestation in women who developed subsequent preeclampsia.32 A study of 126 preeclamptic women found that first trimester free leptin index was significantly elevated compared with 289 controls (P<0.001).33 The largest study to date was nested within a study of pregnancy outcomes, which included 12 804 births in Norway.34 This study included 256 cases of preeclampsia and 607 controls and reported that umbilical cord leptin levels were significantly higher in women with preeclampsia compared with controls after adjustment for gestational age.

Leptin is suggested to play a role in angiogenesis, immunomodulation, and fatty acid metabolism in early placentation.1 Reduced placental perfusion is hypothesized to increase placental expression of leptin, which may increase nutrient delivery to the fetus.5 Studies show that leptin released from the placenta can stimulate system A amino acid transport,35,36 possibly influencing fetal growth. Thus, leptin may be a coping mechanism for reduced placental perfusion and a marker of placental insufficiency. Alternatively, an increase in maternal leptin expression may be a result of other stimuli. Leptin has been shown to play a role in immunity,16 although its function is not completely understood. As an altered immune response is one pathway which may lead to preeclampsia,17 it is possible that inflammatory stimuli or immune dysfunction could alter maternal leptin expression. Once increased, leptin may have direct effects on the development of preeclampsia. In pregnant rats, leptin has been shown to increase blood pressure.15 Leptin has also been shown to be correlated with systolic and diastolic blood pressure in pregnant women, independent of BMI.37 Although 98.4% of placental leptin may be released into the maternal circulation,38 in our study, we cannot determine the proportion placental leptin measured in maternal serum. As placental leptin expression and placental leptin protein are increased in preeclampsia and correlate with circulating levels,5,39 it is suggested that the placenta contributes substantially to serum leptin concentrations. Additionally, leptin is reported to increase throughout pregnancy and then drastically reduces postpartum.40 However, one study found that placental leptin expression is similar in obese and lean women, suggesting that adiposity may increase circulating leptin concentrations during obesity.23

As leptin has been indicated to be a possible marker for early onset preeclampsia (<34 weeks),41 we examined associations between leptin and preeclampsia subtypes. We found that leptin concentrations were significantly higher in term preeclampsia but not preterm preeclampsia. The effect sizes and median leptin levels were similar for term and preterm cases. Among 27 cases of preterm preeclampsia <34 weeks gestation, no significant associations with leptin were observed. We were underpowered to examine the associations with preterm preeclampsia. Larger cohorts with well-defined subtypes are needed to examine these associations.

Obesity is associated with an increased risk of mild and severe forms of preeclampsia,21,22 as well as hyperleptinemia.23 The role of obesity in the pathogenesis of preeclampsia is not clear. It has been suggested that increased leptin, inflammation, and metabolic markers may lead to preeclampsia in obese women.42 We found that leptin could be a possible mediator of BMI and preeclampsia. However, it only accounted for a small percent of the total effect. This suggests that other factors such as increased inflammation in addition to leptin may play a role in obesity-related preeclampsia. Obesity may lead to dysregulation in leptin function that results in maternal disease. Placental leptin resistance is present in maternal obesity because of syncytiotrophoblast downregulation of leptin receptor during states of maternal hyperleptinemia.23 Alternatively, an increase in leptin during obesity may have direct effects on inflammation and blood pressure. The relationship between BMI, leptin, and preeclampsia is likely complex. Future work is needed to explore these relationships.

We obtained data from a large well-defined cohort and were able to adjust for several known risk factors for preeclampsia. This is one of the largest studies examining relationships between serum leptin and preeclampsia. We did not have data on time of diagnosis of preeclampsia. Therefore, some women in our study may have had preeclampsia at the time of blood sampling. However, our results were the same when we examined a smaller gestational age window between 15 and 18 weeks before when preeclampsia would have been diagnosed by a clinician. Still, we cannot rule out the presence of subclinical disease at the time of blood sampling. Diagnostic codes to classify women as having severe or mild preeclampsia were not available for all women in the DNBC. We used gestational age of delivery as a proxy for severe disease and disease onset. This is a common approach,11 but may have limited our ability to assess the role of leptin in preeclampsia severity. As the placenta grows during pregnancy, placental-derived products may increase, and thus, leptin levels may vary by the gestational age of sampling. However, we did not find significant differences in gestational age at sampling between cases and controls. We relied on self-reported BMI, which may be lower than true BMI43 and may bias results of our mediation analysis. Although the in-house assay used to measure leptin was previously validated, a coefficient of variation was not calculated specifically for our study.

Perspectives

Our observational study suggests that serum leptin levels measured in early pregnancy are elevated in women with preeclampsia compared with normotensive controls. Leptin may be a useful biomarker for predicting preeclampsia and could be used clinically as a screening tool in early pregnancy. However, additional studies are needed before assessing its clinical utility. First, these results need to be replicated in an independent cohort. Studies using both circulating and placental expression of leptin would be useful to gain more insight into the role of leptin in preeclampsia pathogenesis. Additionally, further prospective studies with larger samples of women recruited before or early in gestation are needed to confirm whether this relationship is temporal. Finally, the relationship between leptin, BMI, and preeclampsia requires further examination.

Sources of Funding

R01HD048669 from the National Institute of Allergy and Infectious Diseases (C. Haggerty).

Disclosures

None.

  • Received May 30, 2014.
  • Revision received June 24, 2014.
  • Accepted November 25, 2014.
  • © 2014 American Heart Association, Inc.

References

  1. 1.↵
    1. Miehle K,
    2. Stepan H,
    3. Fasshauer M
    . Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia. Clin Endocrinol (Oxf). 2012;76:2–11. doi: 10.1111/j.1365-2265.2011.04234.x.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Masuzaki H,
    2. Ogawa Y,
    3. Sagawa N,
    4. Hosoda K,
    5. Matsumoto T,
    6. Mise H,
    7. Nishimura H,
    8. Yoshimasa Y,
    9. Tanaka I,
    10. Mori T,
    11. Nakao K
    . Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med. 1997;3:1029–1033.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Hauguel-de Mouzon S,
    2. Lepercq J,
    3. Catalano P
    . The known and unknown of leptin in pregnancy. Am J Obstet Gynecol. 2006;194:1537–1545.
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Herse F,
    2. Bai Y,
    3. Staff AC,
    4. Yong-Meid J,
    5. Dechend R,
    6. Zhou R
    . Circulating and uteroplacental adipocytokine concentrations in preeclampsia. Reprod Sci. 2009;16:584–590. doi: 10.1177/1933719109332828.
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Laivuori H,
    2. Gallaher MJ,
    3. Collura L,
    4. Crombleholme WR,
    5. Markovic N,
    6. Rajakumar A,
    7. Hubel CA,
    8. Roberts JM,
    9. Powers RW
    . Relationships between maternal plasma leptin, placental leptin mRNA and protein in normal pregnancy, pre-eclampsia and intrauterine growth restriction without pre-eclampsia. Mol Hum Reprod. 2006;12:551–556. doi: 10.1093/molehr/gal064.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Hendler I,
    2. Blackwell SC,
    3. Mehta SH,
    4. Whitty JE,
    5. Russell E,
    6. Sorokin Y,
    7. Cotton DB
    . The levels of leptin, adiponectin, and resistin in normal weight, overweight, and obese pregnant women with and without preeclampsia. Am J Obstet Gynecol. 2005;193(3 Pt 2):979–983. doi: 10.1016/j.ajog.2005.06.041.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Masuyama H,
    2. Segawa T,
    3. Sumida Y,
    4. Masumoto A,
    5. Inoue S,
    6. Akahori Y,
    7. Hiramats Y
    . Different profiles of circulating angiogenic factors and adipocytokines between early- and late-onset pre-eclampsia. BJOG. 2010;117:314–320. doi: 10.1111/j.1471-0528.2009.02453.x.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Ouyang Y,
    2. Chen H,
    3. Chen H
    . Reduced plasma adiponectin and elevated leptin in pre-eclampsia. Int J Gynaecol Obstet. 2007;98:110–114. doi: 10.1016/j.ijgo.2007.04.021.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Sharma A,
    2. Satyam A,
    3. Sharma JB
    . Leptin, IL-10 and inflammatory markers (TNF-alpha, IL-6 and IL-8) in pre-eclamptic, normotensive pregnant and healthy non-pregnant women. Am J Reprod Immunol. 2007;58:21–30. doi: 10.1111/j.1600-0897.2007.00486.x.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Hutcheon JA,
    2. Lisonkova S,
    3. Joseph KS
    . Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol. 2011;25:391–403. doi: 10.1016/j.bpobgyn.2011.01.006.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Staff AC,
    2. Benton SJ,
    3. von Dadelszen P,
    4. Roberts JM,
    5. Taylor RN,
    6. Powers RW,
    7. Charnock-Jones DS,
    8. Redman CW
    . Redefining preeclampsia using placenta-derived biomarkers. Hypertension. 2013;61:932–942. doi: 10.1161/HYPERTENSIONAHA.111.00250.
    OpenUrlFREE Full Text
  12. 12.↵
    1. Redman CW,
    2. Sargent IL
    . Latest advances in understanding preeclampsia. Science. 2005;308:1592–1594. doi: 10.1126/science.1111726.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    1. Redman CW,
    2. Sargent IL
    . Placental stress and pre-eclampsia: a revised view. Placenta. 2009;30 Suppl A:S38–S42. doi: 10.1016/j.placenta.2008.11.021.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Hiraoka J,
    2. Hosoda K,
    3. Ogawa Y,
    4. Ikeda K,
    5. Nara Y,
    6. Masuzaki H,
    7. Takaya K,
    8. Nakagawa K,
    9. Mashimo T,
    10. Sawamura M,
    11. Koletsky RJ,
    12. Yamori Y,
    13. Nakao K
    . Augmentation of obese (ob) gene expression and leptin secretion in obese spontaneously hypertensive rats (obese SHR or Koletsky rats). Biochem Biophys Res Commun. 1997;231:582–585. doi: 10.1006/bbrc.1997.6145.
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Ibrahim HS,
    2. Omar E,
    3. Froemming GR,
    4. Singh HJ
    . Leptin increases blood pressure and markers of endothelial activation during pregnancy in rats. Biomed Res Int. 2013;2013:298401. doi: 10.1155/2013/298401.
    OpenUrlPubMed
  16. 16.↵
    1. Matarese G,
    2. Moschos S,
    3. Mantzoros CS
    . Leptin in immunology. J Immunol. 2005;174:3137–3142.
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    1. Redman CW,
    2. Sargent IL
    . Immunology of pre-eclampsia. Am J Reprod Immunol. 2010;63:534–543. doi: 10.1111/j.1600-0897.2010.00831.x.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Acromite M,
    2. Ziotopoulou M,
    3. Orlova C,
    4. Mantzoros C
    . Increased leptin levels in preeclampsia: associations with BMI, estrogen and SHBG levels. Hormones (Athens). 2004;3:46–52.
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Dalamaga M,
    2. Srinivas SK,
    3. Elovitz MA,
    4. Chamberland J,
    5. Mantzoros CS
    . Serum adiponectin and leptin in relation to risk for preeclampsia: results from a large case-control study. Metabolism. 2011;60:1539–1544. doi: 10.1016/j.metabol.2011.03.021.
    OpenUrlCrossRefPubMed
  20. 20.↵
    1. Kaaja R,
    2. Laivuori H,
    3. Pulkki P,
    4. Tikkanen MJ,
    5. Hiilesmaa V,
    6. Ylikorkala O
    . Is there any link between insulin resistance and inflammation in established preeclampsia? Metabolism. 2004;53:1433–1435.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Bodnar LM,
    2. Catov JM,
    3. Klebanoff MA,
    4. Ness RB,
    5. Roberts JM
    . Prepregnancy body mass index and the occurrence of severe hypertensive disorders of pregnancy. Epidemiology. 2007;18:234–239. doi: 10.1097/01.ede.0000254119.99660.e7.
    OpenUrlCrossRefPubMed
  22. 22.↵
    1. Bodnar LM,
    2. Ness RB,
    3. Markovic N,
    4. Roberts JM
    . The risk of preeclampsia rises with increasing prepregnancy body mass index. Ann Epidemiol. 2005;15:475–482. doi: 10.1016/j.annepidem.2004.12.008.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Farley DM,
    2. Choi J,
    3. Dudley DJ,
    4. Li C,
    5. Jenkins SL,
    6. Myatt L,
    7. Nathanielsz PW
    . Placental amino acid transport and placental leptin resistance in pregnancies complicated by maternal obesity. Placenta. 2010;31:718–724. doi: 10.1016/j.placenta.2010.06.006.
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Haggerty CL,
    2. Panum I,
    3. Uldum SA,
    4. Bass DC,
    5. Olsen J,
    6. Darville T,
    7. Eastman JM,
    8. Simhan HN,
    9. Roberts JM,
    10. Ness RB
    . Chlamydia trachomatis infection may increase the risk of preeclampsia. Preg Hyperten. 2013;3:28–33.
    OpenUrl
  25. 25.↵
    1. Olsen J,
    2. Melbye M,
    3. Olsen SF,
    4. Sørensen TI,
    5. Aaby P,
    6. Andersen AM,
    7. Taxbøl D,
    8. Hansen KD,
    9. Juhl M,
    10. Schow TB,
    11. Sørensen HT,
    12. Andresen J,
    13. Mortensen EL,
    14. Olesen AW,
    15. Søndergaard C
    . The Danish National Birth Cohort–its background, structure and aim. Scand J Public Health. 2001;29:300–307.
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. Klemmensen AK,
    2. Olsen SF,
    3. Osterdal ML,
    4. Tabor A
    . Validity of preeclampsia-related diagnoses recorded in a national hospital registry and in a postpartum interview of the women. Am J Epidemiol. 2007;166:117–124. doi: 10.1093/aje/kwm139.
    OpenUrlAbstract/FREE Full Text
  27. 27.↵
    1. Myatt L,
    2. Redman CW,
    3. Staff AC,
    4. Hansson S,
    5. Wilson ML,
    6. Laivuori H,
    7. Poston L,
    8. Roberts JM
    ; Global Pregnancy CoLaboratory. Strategy for standardization of preeclampsia research study design. Hypertension. 2014;63:1293–1301. doi: 10.1161/HYPERTENSIONAHA.113.02664.
    OpenUrlAbstract/FREE Full Text
  28. 28.↵
    1. Skogstrand K,
    2. Thorsen P,
    3. Nørgaard-Pedersen B,
    4. Schendel DE,
    5. Sørensen LC,
    6. Hougaard DM
    . Simultaneous measurement of 25 inflammatory markers and neurotrophins in neonatal dried blood spots by immunoassay with xMAP technology. Clin Chem. 2005;51:1854–1866. doi: 10.1373/clinchem.2005.052241.
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    1. Madsen EL,
    2. Bruun JM,
    3. Skogstrand K,
    4. Hougaard DM,
    5. Christiansen T,
    6. Richelsen B
    . Long-term weight loss decreases the nontraditional cardiovascular risk factors interleukin-18 and matrix metalloproteinase-9 in obese subjects. Metabolism. 2009;58:946–953. doi: 10.1016/j.metabol.2009.02.031.
    OpenUrlCrossRefPubMed
  30. 30.↵
    1. Uh HW,
    2. Hartgers FC,
    3. Yazdanbakhsh M,
    4. Houwing-Duistermaat JJ
    . Evaluation of regression methods when immunological measurements are constrained by detection limits. BMC Immunol. 2008;9:59. doi: 10.1186/1471-2172-9-59.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Jasti S,
    2. Dudley WN,
    3. Goldwater E
    . SAS macros for testing statistical mediation in data with binary mediators or outcomes. Nurs Res. 2008;57:118–122. doi: 10.1097/01.NNR.0000313479.55002.74.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Clausen T,
    2. Djurovic S,
    3. Reseland JE,
    4. Berg K,
    5. Drevon CA,
    6. Henriksen T
    . Altered plasma concentrations of leptin, transforming growth factor-beta(1) and plasminogen activator inhibitor type 2 at 18 weeks of gestation in women destined to develop pre-eclampsia. Circulating markers of disturbed placentation? Placenta. 2002;23:380–385. doi: 10.1053/plac.2002.0828.
    OpenUrlCrossRefPubMed
  33. 33.↵
    1. Hedley PL,
    2. Placing S,
    3. Wøjdemann K,
    4. Carlsen AL,
    5. Shalmi AC,
    6. Sundberg K,
    7. Tabor A,
    8. Christiansen M
    . Free leptin index and PAPP-A: a first trimester maternal serum screening test for pre-eclampsia. Prenat Diagn. 2010;30:103–109. doi: 10.1002/pd.2337.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Odegård RA,
    2. Vatten LJ,
    3. Nilsen ST,
    4. Salvesen KA,
    5. Austgulen R
    . Umbilical cord plasma leptin is increased in preeclampsia. Am J Obstet Gynecol. 2002;186:427–432.
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Jansson N,
    2. Greenwood SL,
    3. Johansson BR,
    4. Powell TL,
    5. Jansson T
    . Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments. J Clin Endocrinol Metab. 2003;88:1205–1211. doi: 10.1210/jc.2002-021332.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. von Versen-Höynck F,
    2. Rajakumar A,
    3. Parrott MS,
    4. Powers RW
    . Leptin affects system A amino acid transport activity in the human placenta: evidence for STAT3 dependent mechanisms. Placenta. 2009;30:361–367. doi: 10.1016/j.placenta.2009.01.004.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Buhling KJ,
    2. Harder T,
    3. Sehouli J,
    4. Nanz J,
    5. Plagemann A,
    6. Dudenhausen JW
    . Independent association between leptin and blood pressure during third trimester in normal and gestational diabetic pregnancies. Eur J Obstet Gynecol Reprod Biol. 2005;119:180–184. doi: 10.1016/j.ejogrb.2004.07.006.
    OpenUrlCrossRefPubMed
  38. 38.↵
    1. Linnemann K,
    2. Malek A,
    3. Sager R,
    4. Blum WF,
    5. Schneider H,
    6. Fusch C
    . Leptin production and release in the dually in vitro perfused human placenta. J Clin Endocrinol Metab. 2000;85:4298–4301. doi: 10.1210/jcem.85.11.6933.
    OpenUrlCrossRefPubMed
  39. 39.↵
    1. Lepercq J,
    2. Challier JC,
    3. Guerre-Millo M,
    4. Cauzac M,
    5. Vidal H,
    6. Hauguel-de Mouzon S
    . Prenatal leptin production: evidence that fetal adipose tissue produces leptin. J Clin Endocrinol Metab. 2001;86:2409–2413. doi: 10.1210/jcem.86.6.7529.
    OpenUrlCrossRefPubMed
  40. 40.↵
    1. Hardie L,
    2. Trayhurn P,
    3. Abramovich D,
    4. Fowler P
    . Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy. Clin Endocrinol. 1997;47:101–106.
    OpenUrlCrossRefPubMed
  41. 41.↵
    1. Weedon-Fekjær MS,
    2. Sheng Y,
    3. Sugulle M,
    4. Johnsen GM,
    5. Herse F,
    6. Redman CW,
    7. Lyle R,
    8. Dechend R,
    9. Staff AC
    . Placental miR-1301 is dysregulated in early-onset preeclampsia and inversely correlated with maternal circulating leptin. Placenta. 2014;35:709–717. doi: 10.1016/j.placenta.2014.07.002.
    OpenUrlCrossRefPubMed
  42. 42.↵
    1. Roberts JM,
    2. Bodnar LM,
    3. Patrick TE,
    4. Powers RW
    . The role of obesity in preeclampsia. Preg Hypertens. 2011;1:6–16. doi: 10.1016/j.preghy.2010.10.013.
    OpenUrl
  43. 43.↵
    1. Russell A,
    2. Gillespie S,
    3. Satya S,
    4. Gaudet LM
    . Assessing the accuracy of pregnant women in recalling pre-pregnancy weight and gestational weight gain. J Obstet Gynaecol Can. 2013;35:802–809.
    OpenUrlPubMed

Novelty and Significance

What Is New?

  • This is the largest study to examine serum leptin in early pregnancy (9–26 weeks gestation) and its relationship to preeclampsia defined by severity.

What Is Relevant?

  • Serum leptin measured in early pregnancy (9–26 weeks gestation) is elevated in preeclampsia.

  • Serum leptin may mediate some of the relationship between body mass index and preeclampsia.

Summary

Elevated maternal serum leptin measured in early pregnancy is associated with preeclampsia.

View Abstract
Back to top
Previous ArticleNext Article

This Issue

Hypertension
March 2015, Volume 65, Issue 3
  • Table of Contents
Previous ArticleNext Article

Jump to

  • Article
    • Abstract
    • Introduction
    • Methods
    • Results
    • Discussion
    • Sources of Funding
    • Disclosures
    • References
  • Figures & Tables
  • Info & Metrics
  • eLetters

Article Tools

  • Print
  • Citation Tools
    Serum Leptin Measured in Early Pregnancy Is Higher in Women With Preeclampsia Compared With Normotensive Pregnant WomenNovelty and Significance
    Brandie D. Taylor, Roberta B. Ness, Jørn Olsen, David M. Hougaard, Kristin Skogstrand, James M. Roberts and Catherine L. Haggerty
    Hypertension. 2015;65:594-599, originally published December 15, 2014
    https://doi.org/10.1161/HYPERTENSIONAHA.114.03979

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
  • Article Alerts
    Log in to Email Alerts with your email address.
  • Save to my folders

Share this Article

  • Email

    Thank you for your interest in spreading the word on Hypertension.

    NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

    Enter multiple addresses on separate lines or separate them with commas.
    Serum Leptin Measured in Early Pregnancy Is Higher in Women With Preeclampsia Compared With Normotensive Pregnant WomenNovelty and Significance
    (Your Name) has sent you a message from Hypertension
    (Your Name) thought you would like to see the Hypertension web site.
  • Share on Social Media
    Serum Leptin Measured in Early Pregnancy Is Higher in Women With Preeclampsia Compared With Normotensive Pregnant WomenNovelty and Significance
    Brandie D. Taylor, Roberta B. Ness, Jørn Olsen, David M. Hougaard, Kristin Skogstrand, James M. Roberts and Catherine L. Haggerty
    Hypertension. 2015;65:594-599, originally published December 15, 2014
    https://doi.org/10.1161/HYPERTENSIONAHA.114.03979
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo

Related Articles

Cited By...

Subjects

  • Cardiology
    • Etiology
      • Hypertension
        • Hypertension

Hypertension

  • About Hypertension
  • Instructions for Authors
  • AHA CME
  • Guidelines and Statements
  • Permissions
  • Journal Policies
  • Email Alerts
  • Open Access Information
  • AHA Journals RSS
  • AHA Newsroom

Editorial Office Address:
7272 Greenville Ave.
Dallas, TX 75231
email: hypertension@heart.org

Information for:
  • Advertisers
  • Subscribers
  • Subscriber Help
  • Institutions / Librarians
  • Institutional Subscriptions FAQ
  • International Users
American Heart Association Learn and Live
National Center
7272 Greenville Ave.
Dallas, TX 75231

Customer Service

  • 1-800-AHA-USA-1
  • 1-800-242-8721
  • Local Info
  • Contact Us

About Us

Our mission is to build healthier lives, free of cardiovascular diseases and stroke. That single purpose drives all we do. The need for our work is beyond question. Find Out More about the American Heart Association

  • Careers
  • SHOP
  • Latest Heart and Stroke News
  • AHA/ASA Media Newsroom

Our Sites

  • American Heart Association
  • American Stroke Association
  • For Professionals
  • More Sites

Take Action

  • Advocate
  • Donate
  • Planned Giving
  • Volunteer

Online Communities

  • AFib Support
  • Garden Community
  • Patient Support Network
  • Professional Online Network

Follow Us:

  • Follow Circulation on Twitter
  • Visit Circulation on Facebook
  • Follow Circulation on Google Plus
  • Follow Circulation on Instagram
  • Follow Circulation on Pinterest
  • Follow Circulation on YouTube
  • Rss Feeds
  • Privacy Policy
  • Copyright
  • Ethics Policy
  • Conflict of Interest Policy
  • Linking Policy
  • Diversity
  • Careers

©2018 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. The American Heart Association is a qualified 501(c)(3) tax-exempt organization.
*Red Dress™ DHHS, Go Red™ AHA; National Wear Red Day ® is a registered trademark.

  • PUTTING PATIENTS FIRST National Health Council Standards of Excellence Certification Program
  • BBB Accredited Charity
  • Comodo Secured