Background
Despite decades of research, and much progress in discernment of biomarkers in the
maternal circulation, the pathogenesis of preeclampsia (PE) remains elusive. The pathophysiology
of PE is believed to involve aberrant placentation and an associated increase in systemic
inflammation. In this conceptualization, PE becomes more likely when the level of
systemic inflammatory burden inherent in pregnancy itself exceeds the maternal capacity
to compensate for this additional stress. If this is the case, then it is possible
to hypothesize that conditions, such as infectious disease, that increase systemic
inflammatory burden should also increase the risk of PE. As urinary tract infection
(UTI) represents a common source of inflammation during pregnancy, we tested whether
presence of UTI during pregnancy increased the odds of developing PE. Prior work has
documented this association. However many of these studies were limited by small cohort
sizes and insufficient control for covariates.
Objective
The present study is a secondary analysis of a robust contemporary obstetrical cohort
recruited to examine the ability of longitudinally sampled maternal angiogenic concentrations
to predict PE. We hypothesize that the occurrence of UTI during a pregnancy is associated
with the later occurrence of PE in that pregnancy. As PE is believed to be associated
with aberrations in systemic angiogenic levels (placental growth factor and soluble
isoform of VEGF receptor), we further hypothesize that there will be significant interactions
between maternal angiogenic protein levels and the occurrence of UTI.
Study Design
Women aged ≥18 years (n = 2607) were recruited and followed up prospectively from
the initiation of prenatal care through delivery at 3 regional academic centers. PE
was defined by American Congress of Obstetricians and Gynecologists criteria and was
independently validated by a panel of physicians. UTI was defined by the presence
of clinical symptoms necessitating treatment in addition to supportive laboratory
evidence. Multivariate logistic regression models were used and controlled for maternal
age, race, parity, body mass index, hypertension, diabetes, in vitro fertilization,
and smoking status.
Results
There were 129 women with diagnosed UTIs and 235 with PE. Patients with UTI in pregnancy
had higher rates of PE (31.1% vs 7.8%, P < .001) compared to those without reported UTI. The mean gestational age (SD) for
UTI diagnosis in PE cases and controls was 25.6 (10.4) and 21.9 (10.9) weeks, respectively
(P = .08). The unadjusted odds ratio for PE in the setting of UTI was 5.29 (95% confidence
interval, 3.54–7.89). After controlling for confounders, UTI was associated with an
odds ratio for PE of 3.2 (95% confidence interval, 2.0–5.1).
Conclusion
Presence of UTI in pregnancy, particularly in the third trimester, is strongly associated
with PE. This association supports the hypothesis that the risk of PE is enhanced
by an increased maternal inflammatory burden. Prophylaxis against UTI represents a
potentially low-cost global intervention to slow or halt the development of PE.
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Article info
Publication history
Published online: October 05, 2015
Accepted:
September 28,
2015
Received in revised form:
September 23,
2015
Received:
July 20,
2015
Footnotes
This research was supported by an unrestricted grant from Abbott Diagnostics Division (9MZ-04-06N03).
The authors report no conflict of interest.
Separate portions of analysis previously presented as a poster at the annual meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, Feb. 13, 2012, and as a poster (abstract T-182) at the Society for Gynecologic Investigation, Florence, Italy, March 27, 2014.
Cite this article as: Easter SR, Cantonwine DE, Zera CA, et al. Urinary tract infection during pregnancy, angiogenic factor profiles, and risk of preeclampsia. Am J Obstet Gynecol 2016;214:387.e1-7.
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