Maternal infection and risk of preeclampsia: Systematic review and metaanalysis

doi:10.1016/j.ajog.2007.07.040

American Journal of Obstetrics and Gynecology

Volume 198, Issue 1, January 2008, Pages 7-22

https://doi.org/10.1016/j.ajog.2007.07.040 Get rights and content

There are lingering questions regarding the association between maternal infection and preeclampsia. Systematic review and metaanalysis was conducted of observational studies that examined the relationship between maternal infection and preeclampsia. Forty-nine studies met the inclusion criteria. The risk of preeclampsia was increased in pregnant women with urinary tract infection (pooled odds ratio, 1.57; 95% CI, 1.45-1.70) and periodontal disease (pooled odds ratio, 1.76; 95% CI, 1.43-2.18). There were no associations between preeclampsia and presence of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus, treated and nontreated HIV infection, and malaria. Individual studies did not find a relationship between herpes simplex virus type 2, bacterial vaginosis, and Mycoplasma hominis and preeclampsia. Urinary tract infection and periodontal disease during pregnancy are associated with an increased risk of preeclampsia. More studies are required to verify this as well as to explore whether or not such relationships are causal and, if so, the mechanisms involved.

Section snippets

Materials and Methods

The systematic review was conducted following a prospectively prepared protocol and reported using the Metaanalysis of Observational Studies in Epidemiology (MOOSE) guidelines for metaanalysis of observational studies.⁹

An initial search was performed in MEDLINE, EMBASE, POPLINE, CINAHL, and LILACS (all from inception to June 30, 2007) to identify potentially eligible studies. We applied the following algorithm both in MeSH and in free-text words: (infection OR inflammation) AND (preeclampsia OR

Results

The searches produced 1816 citations of which 88 were considered relevant (77 through computer search, and 11 from references cited in articles). Thirty-nine studies were excluded, mainly because they lacked data relating maternal infection and preeclampsia (79%) or included women without proteinuria in the preeclampsia group (13%). References for excluded studies can be obtained from the authors. Forty-nine studies (27 case-control, 19 cohort, and 3 cross-sectional)16, 17, 18, 19, 20, 21, 22,

Comment

Our study, using the most rigorous methodology for performing systematic reviews of observational studies, demonstrates that both urinary tract infection and periodontal disease during pregnancy are associated with an increased risk of preeclampsia. Moreover, there is some evidence suggesting that treating urinary tract infections during pregnancy reduces the incidence of preeclampsia. These data support the hypothesis that infection may play a causal role in the development of preeclampsia or

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In preeclampsia, the pattern would be increased TLR2, TLR3, TLR4 as well as TLR8 (the latter for early-onset disease only) and reduced RIG-1. The importance of this distinction is highlighted by studies that have indicated that maternal infection, especially in the urinary tract, that does not involve the neonate can be associated with preeclampsia [40]. Finally, the study strongly suggests that the diagnostic pathologist must rely on molecular and not histologic findings to diagnose most cases of in utero infection; some viruses such as CMV can produce specific inclusions but these are rare.
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: Reprints not available from the authors.

: This study was supported by the United Nations Development Programme/United Nations Population Fund/World Health Organization/World Bank Special Program of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland.

: The views expressed in this document are solely the responsibility of the authors and do not necessarily represent the views of the World Health Organization or its Member States.

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ReviewObstetricsMaternal infection and risk of preeclampsia: Systematic review and metaanalysis

Section snippets

Materials and Methods

Results

Comment

Int J Gynaecol Obstet

Med Hypotheses

Am J Obstet Gynecol

Lancet

Lancet

Int J Gynaecol Obstet

Int J Gynaecol Obstet

Am J Obstet Gynecol

Obstet Gynecol

Obstet Gynecol

Obstet Gynecol

BJOG

Int J Gynaecol Obstet

Am J Pathol

Lancet

Int J Gynaecol Obstet

Eur J Obstet Gynecol Reprod Biol

Lancet

Obstet Gynecol

Placenta

Am J Obstet Gynecol

Lancet

Am J Obstet Gynecol

Lancet

Risk factors for preeclampsia in a large cohort of Latin American and Caribbean women

BJOG

Summary of the NHLBI working group on research on hypertension during pregnancy

Hypertension

Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia

Hypertension

Latest advances in understanding preeclampsia

Science

Could an infectious trigger explain the differential maternal response to the shared placental pathology of preeclampsia and normotensive intrauterine growth restriction?

Acta Obstet Gynecol Scand

Users’ guides to the medical literature. IVHow to use an article about harm. Evidence-Based Medicine Working Group

JAMA

Meta-analysis of observational studies in epidemiology: a proposal for reportingMeta-analysis Of Observational Studies in Epidemiology (MOOSE) group

JAMA

The environment and disease: association or causation?

Proc R Soc Med

Biologic plausibility in causal inference: current method and practice

Am J Epidemiol

The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions

J Epidemiol Community Health

A comparison of several point estimators of the odds ratio in a single 2 x 2 contingency table

Biometrics

Measuring inconsistency in meta-analyses

BMJ

Bias in meta-analyses detected by a simple graphical test

BMJ

Asymptomatic bacteriuria in pregnancy and its association with prematurity

J Lab Clin Med

Bacteriuria, prematurity, and the hypertensive disorders of pregnancy

BMJ

The effects of bacteriuria in pregnancy on maternal and fetal health

Kidney Int

Review
Obstetrics
Maternal infection and risk of preeclampsia: Systematic review and metaanalysis