Psychological Stress and Hepcidin: A Potential Link to

Preterm BirthMary Dawn Hennessy, RN PhD

Department of Women, Children, and Family Health Science

University of Illinois at Chicago

Carmen Giurgescu, RN PhD WHNPWayne State University

Elizabeta Nemeth, PhDDepartment of Medicine

University of California, Los Angeles

Background and Significance

In 2009, 18% of US African American delivered preterm (<37 weeks)

African Americans have increased psychological stress and higher rates of iron deficiency

Conflicting evidence on link between iron deficiency and preterm birth

Inflammation-mediated iron restriction may be a risk factor, but studies have not made distinction

Spleen

Bone marrow

RBC

Liver

Duodenum

PlasmaFe-Tf

0-5 mg/d

1-2 mg/d 20 mg/d

20 m

g/d

Fpn

Fpn

Fpn

hepcidinhepcidin

hepcidin

Hepcidin: Key Regulator of Iron

Regulation of hepcidin production

Spleen

Bone marrow

RBC

Liver

Duodenum

PlasmaFe-Tf

Fpn

Fpn

Fpn

hepcidinhepcidin

hepcidin

Erythropoietic signal

Iron signal

Inflammation

Aims

Aim 1. Determine if psychological stress and inflammation are correlated with hepcidin levels during pregnancy

Aim 2. Determine if hepcidin levels during pregnancy predict preterm birth

Hypotheses

Hypothesis 1. At any time point during pregnancy, increased psychological stress and/or inflammation will be correlated with increasing hepcidin levels

Hypothesis 2. At any time point during pregnancy, increased hepcidin will be predictive of preterm birth

Sample

88 pregnant self-identified African Americans

Predominately low-income from a large Midwest city

At least 18 years of age Singleton pregnancy 16-22 weeks gestation

Design

Descriptive, longitudinal design Data collected at

– T1 16-22 weeks

– T2 26-32 weeks

– T3 birth

Psychological Stress Measures

Perceived racial discrimination (EOD) Personal resources

– Optimism (LOT)– Self-esteem (RSES)– Coping (PCI)

Emotional stress response– Distress (PGWB)– Anxiety (State Anxiety subscale)– Depression (CES-D)

Serum Measures

Inflammation by multiplex bead immunoassays– Interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-

8, IL-10– TNF-α– C-reactive protein

Hepcidin by ELISA

Results – Demographic and Clinical Characteristics

Characteristic Total sample n = 88, mean (SD)

Age (years) 24 (5.29)

Gestational age at T1 (weeks) 20 (2.50)

Gestational age at T2 (weeks) 29 (2.68)

Gestational age at birth (weeks) 38.8 (2.65)

Birth weight (grams) 3,148 (717)

Low birth weight (< 2,500 grams) 17%

Preterm birth (< 37 weeks) 7%

Single 82%

Unemployed 52%

Household Income < $10,000/year 50%

Note: T1 = 16 - 22 weeks, T2 = 26 - 32 weeks

Results – Psychological Stress, Inflammation and Hepcidin

Hepcidin T1 Hepcidin T2

Experiences of Discrimination- Situations T1

r = 0.22; p = .04

Experiences of Discrimination- Frequency T1

r = 0.25; p = .02

Life Orientation Test T1 r = -0.22; p = .04

IL-8 T2 r = 0.26; p = .05

Note: T1 = 16 - 22 weeks, T2 = 26 - 32 weeksIL = interleukin

Results – Hepcidin and Preterm Birth

Hepcidin ng/mL Full Term Birth

Preterm Birth

Total

T1 < 14 and T2 < 11 29 (44%) 1 (20%) 30 (42%)

T1 < 14 and T2 > 11 5 (8%) 2 (40%) 7 (10%)

T1 > 14 and T2 < 11

21 (32%) 0 (0%) 21 (30%)

T1 > 14 and T2 > 11 11 (17%) 2 (40%) 13 (18%)

Total 66 5 71

Χ2 = 8.56; p = .036

Note: T1 = 16 - 22 weeks, T2 = 26 - 32 weeks

Results – Hepcidin Levels and Preterm Birth

Total Sample

Full Term Birth

Preterm Birth

Test Statistic

Hepcidin

(ng/mL) T1 mean (SD)

17.8 (19.3)n = 88

17.5 (19.7)n = 81

21.5 (13.7)n = 7

F (1,86) = 0.27; p = .60

Hepcidin

(ng/mL) T2

mean (SD)

8.68 (12.2)n = 76

7.88 (11.7)n = 71

20.0 (15.0)n = 5

F (1,74) = 4.88; p = .03

Note: T1 = 16 - 22 weeks, T2 = 26 - 32 weeks

Results – Hepcidin as a Predictor of Preterm Birth

Preterm Birth

Odds Ratio

Standard Error

z-Score p-value 95% CI

Hepcidin T2 1.06 .029 2.07 .039 1.00 – 1.12

Note: CI = Confidence IntervalT2 = 26 - 32 weeks

Conclusions

The iron-regulatory hormone hepcidin is increased in pregnant women with elevated psychological stress and inflammation

Hepcidin may be a useful biomarker of inflammation/stress during pregnancy

Hepcidin-mediated iron restriction may increase the risk for preterm birth

Future Research

Evaluation of hepcidin throughout pregnancy, as elevated or undetectable hepcidin could be used as an early diagnostic tool and an indicator of inflammation-mediated iron restriction or true iron deficiency

Funding Acknowledgements

Midwest Nursing Research Society New Investigator Seed Grant

The University of Illinois at Chicago Dean’s Fund