Distinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia

Tangerås, Line Haugstad; Austdal, Marie; Skråstad, Ragnhild Bergene; Salvesen, Kjell Å.; Austgulen, Rigmor; Bathen, Tone Frost; Iversen, Ann‐Charlotte

doi:10.1161/atvbaha.115.305817

Cited by 42 publications

(47 citation statements)

References 54 publications

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“…The risk of preterm delivery, for example, was found in one study to be 7.2% in normotensive women, 12.5% in women with GH, and 39.2% in those with preeclampsia 17. Evidence also shows that the inflammatory signature may be distinct in women with GH compared with preeclampsia, with the possibility that women with GH can compensate more successfully 18. In contrast, preeclampsia is more often associated with placental disease characterized by impaired markers of angiogenesis 19.…”

Section: Pathophysiology and Risk Factorsmentioning

confidence: 99%

Hypertensive Disorders of Pregnancy and Future Maternal Cardiovascular Risk

Ying

Catov

Ouyang

2018

JAHA

178

119

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Section: Pathophysiology and Risk Factorsmentioning

confidence: 99%

Hypertensive Disorders of Pregnancy and Future Maternal Cardiovascular Risk

Ying

Catov

Ouyang

2018

JAHA

178

119

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“…Only preeclampsia occurs more often in first pregnancies 15. Differences in the pathophysiology between the 2 disorders are indicated by higher serum cytokine levels in the early phase of GH and stronger involvement of placental dysfunction in preeclampsia 12, 16, 17, 18…”

Section: Introductionmentioning

confidence: 99%

Association Between Gestational Hypertension and Risk of Cardiovascular Disease Among 617 589 Norwegian Women

Riise

Sulo

Tell

et al. 2018

JAHA

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BackgroundPreeclampsia and gestational hypertension (GH) are the most common hypertensive pregnancy disorders. Preeclampsia has been linked to increased risk of cardiovascular disease (CVD), but a similar association for GH has not been established. We aimed to determine the association between GH and subsequent CVD, and explore the additional role of small‐for‐gestational‐age infants, preterm delivery, and parity.Methods and ResultsData from the Medical Birth Registry of Norway were linked to the Cardiovascular Disease in Norway project and the Norwegian Cause of Death Registry. Hazard ratios and 95% confidence intervals were computed using Cox proportional hazard regression, comparing women with and without GH during their first and/or second pregnancy. We included all women with a first delivery from 1980 through 2009 (n=617 589) and followed them for a median of 14.3 (quartile 1–quartile 3: 6.9–21.5) years. Women with GH in the first pregnancy had 1.8‐fold (95% confidence interval, 1.7–2.0) higher risk of subsequent CVD compared with women without any hypertensive pregnancy disorder. When GH occurred in combination with small‐for‐gestational‐age infants and/or preterm delivery, the hazard ratio was 2.6 (95% confidence interval, 2.3–3.0). When women with GH were compared with women with preeclampsia, the risk of CVD was comparable when the pregnancy complications occurred in either the first or second pregnancy but was significantly higher for preeclampsia without complications when the disorder occurred in both pregnancies.Conclusions GH was associated with increased risk of subsequent CVD, and the highest risk was observed when GH was combined with small‐for‐gestational‐age infants and/or preterm delivery.

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“…It is certainly plausible that an impaired inflammatory immune response during pregnancy may contribute to the development of spontaneously initiated early birth as well as complications of pregnancy that increase risk for medically-indicated early birth. For example, while this study excluded women with preeclampsia due to known inflammatory features, a growing body of literature implicates inflammation in additional hypertensive disorders (Li et al, 2016; Tangerås et al, 2015). The role of IL1RN and IL-1β inhibition in the development of various complications of pregnancy with hypothesized immune components is worth exploring.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing

et al. 2017

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Background Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN) gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests inflammatory pathways differ by race; however, studies among African American women are lacking. Objectives We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1β production. Methods A candidate gene study using a prospective cohort design was used. We collected blood samples at 28–32 weeks gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN SNP rs2637988 was genotyped and lipopolysaccharide-stimulated IL-1Ra and IL-1β production quantified. Medical record review determined timing of birth. Results Women with GG genotype gave birth earlier than women with AA/AG genotypes (b* = 0.21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [-0.05, 0.13]. Women with GG genotype demonstrated less inhibition of IL-1β production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = 0.93, p = .03). Greater IL-1β production at 28–32 weeks of pregnancy was marginally associated with earlier birth (b* = 0.21, p = .05). Discussion Women with GG genotype may be at risk for earlier birth due to diminished IL-1β inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions.

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Distinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia

Cited by 42 publications

References 54 publications

Hypertensive Disorders of Pregnancy and Future Maternal Cardiovascular Risk

Hypertensive Disorders of Pregnancy and Future Maternal Cardiovascular Risk

Association Between Gestational Hypertension and Risk of Cardiovascular Disease Among 617 589 Norwegian Women

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing

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