Genetic and non-genetic risk factors for pre-eclampsia: an umbrella review of systematic reviews and meta-analyses of observational studies
File(s)
Author(s)
Giannakou, K
Evangelou, E
Papatheodorou, SI
Type
Journal Article
Abstract
OBJECTIVE: To summarize evidence from the literature on the risk factors associated with preeclampsia, assess the presence of statistical biases and identify associations with robust evidence. METHODS: We searched PubMed and ISI Web of Science from inception to October, 2016, to identify systematic reviews and meta-analyses of observational studies examining associations between genetic and non-genetic risk factors for preeclampsia. For each meta-analysis we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We estimated the between-study heterogeneity expressed by I(2) (considering above 75% as very large), evidence of small-study effects (large studies had significantly more conservative results than smaller studies and evidence of excess significance bias (too many studies with statistically significant results). RESULTS: Fifty-seven eligible papers were identified providing data on 130 associations including 1466 primary studies, covering a very wide range of risk factors: co-morbid diseases, genetic factors, exposure to environmental agents and a range of biomarkers. Sixty-five (50%) associations had nominally statistically significant findings at P<0.05, while sixteen (12%) were significant at P<10(-6) . Sixty-four (49%) associations had large or very large heterogeneity. Evidence for small-study effects and excess significance bias was found in ten (8%) and twenty-six (20%) associations, respectively. Oocyte donation vs normal conception (OR 4.33, 95% CI: 3.11-6.03) had >1000 cases, 95% prediction intervals excluding the null, not suggestive of large heterogeneity (I(2) <50%), small-study effects (P for Egger's test>0.10), or excess of significance (P>0.05). Across the statistically significant genetic risk factors (P<0.05), only PAI-1 4G/5G (recessive model) polymorphism was supported with strong evidence for a contribution to the pathogenesis of preeclampsia. Eleven factors (serum iron level, PAPP-A, chronic kidney disease, polycystic ovary syndrome, mental stress, bacterial & viral infections, cigarette smoking, oocyte donation vs assisted reproductive technology, obese vs normal weight women, severe obese vs normal weight women and primiparity) presented highly suggestive evidence for preeclampsia. CONCLUSIONS: A large proportion of meta-analyses of genetic and non-genetic risk factors for preeclampsia have caveats, which threaten their validity. Oocyte donation vs normal conception and PAI-1 4G/5G polymorphism (recessive model) show the strongest consistent evidence.
Date Issued
2018-06-01
Date Acceptance
2017-10-30
Citation
Ultrasound in Obstetrics and Gynecology, 2018, 51 (6), pp.720-730
ISSN
0960-7692
Publisher
Wiley
Start Page
720
End Page
730
Journal / Book Title
Ultrasound in Obstetrics and Gynecology
Volume
51
Issue
6
Copyright Statement
© 2017 ISUOG. Published by John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Giannakou, K., Evangelou, E. and Papatheodorou, S. I. , Genetic and non-genetic risk factors for pre-eclampsia: an umbrella review of systematic reviews and meta-analyses of observational studies. Ultrasound Obstet Gynecol. Accepted Author Manuscript, which has been published in final form at https://dx.doi.org/10.1002/uog.18959. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Subjects
Epidemiology
Meta-analysis
Preeclampsia
Risk factors
Umbrella review
Publication Status
Published
Date Publish Online
2017-11-16