Background
Preeclampsia is a prevalent and enigmatic disease, in part characterized by poor remodeling
of the spiral arteries. However, preeclampsia does not always clinically present when
remodeling has failed to occur. Hypotheses surrounding the “second hit” that is necessary
for the clinical presentation of the disease focus on maternal inflammation and oxidative
stress. Yet, the studies to date that have investigated these factors have used cross-sectional
study designs or small study populations.
Objective
In the present study, we sought to explore longitudinal trajectories, beginning early
in gestation, of a panel of inflammation and oxidative stress markers in women who
went on to have preeclamptic or normotensive pregnancies.
Study Design
We examined 441 subjects from the ongoing LIFECODES prospective birth cohort, which
included 50 mothers who experienced preeclampsia and 391 mothers with normotensive
pregnancies. Participants provided urine and plasma samples at 4 time points during
gestation (median, 10, 18, 26, and 35 weeks) that were analyzed for a panel of oxidative
stress and inflammation markers. Oxidative stress biomarkers included 8-isoprostane
and 8-hydroxydeoxyguanosine. Inflammation biomarkers included C-reactive protein,
the cytokines interleukin-1β, -6, and -10, and tumor necrosis factor-α. We created
Cox proportional hazard models to calculate hazard ratios based on time of preeclampsia
diagnosis in association with biomarker concentrations at each of the 4 study visits.
Results
In adjusted models, hazard ratios of preeclampsia were significantly (P<.01) elevated in association with all inflammation biomarkers that were measured
at visit 2 (median, 18 weeks; hazard ratios, 1.31–1.83, in association with an interquartile
range increase in biomarker). Hazard ratios at this time point were the most elevated
for C-reactive protein, for interleukin-1β, -6, and -10, and for the oxidative stress
biomarker 8-isoprostane (hazard ratio, 1.68; 95% confidence interval, 1.14–2.48) compared
to other time points. Hazard ratios for tumor necrosis factor-α were consistently
elevated at all 4 of the study visits (hazard ratios, 1.49–1.63; P<.01). In sensitivity analyses, we observed that these associations were attenuated
within groups typically at higher risk of experiencing preeclampsia, which include
African American mothers, mothers with higher body mass index at the beginning of
gestation, and pregnancies that ended preterm.
Conclusions
This study provides the most robust data to date on repeated measures of inflammation
and oxidative stress in preeclamptic compared with normotensive pregnancies. Within
these groups, inflammation and oxidative stress biomarkers show different patterns
across gestation, beginning as early as 10 weeks. The start of the second trimester
appears to be a particularly important time point for the measurement of these biomarkers.
Although biomarkers alone do not appear to be useful in the prediction of preeclampsia,
these data are useful in understanding the maternal inflammatory profile in pregnancy
before the development of the disease and may be used to further develop an understanding
of potentially preventative measures.
Key words
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Article Info
Publication History
Published online: December 31, 2016
Accepted:
December 27,
2016
Received in revised form:
December 16,
2016
Received:
September 30,
2016
Footnotes
Supported by the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health , grant numbers: R01ES018872 , P42ES017198 , and P30ES017885 , and by the Intramural Research Program of NIEHS ( ZIAES103321 ). The original cohort was supported by an unrestricted grant from Abbott Diagnostics Division ( 9MZ-04-06N03 ).
The authors report no conflict of interest.
Cite this article as: Ferguson KK, Meeker JD, McElrath TF, et al. Repeated measures of inflammation and oxidative stress biomarkers in preeclamptic and normotensive pregnancies. Am J Obstet Gynecol 2017;216:527.e1-9.
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Published by Elsevier Inc.
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- Ferguson KK, McElrath TF, Chen Y-H, et al. Repeated measures of urinary oxidative stress biomarkers during pregnancy and preterm birth. Am J Obstet Gynecol 2015;212:208.e1-8.American Journal of Obstetrics & GynecologyVol. 221Issue 5
- Oxidative stress and inflammatory biomarkers in normal and preeclamptic pregnanciesAmerican Journal of Obstetrics & GynecologyVol. 217Issue 4
- PreviewI read with interest the article by Ferguson et al,1 which reports on 2 urinary metabolites as indicators of oxidative stress: 8-isoprostane, a marker of lipid peroxidation, and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage. The authors constantly found the 8-isoprostane to be elevated and yet the 8-OHdG to be decreased throughout preeclamptic pregnancy but give no clear explanation to opposing findings.
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