Abstract
Background: IgA nephropathy is the most common primary glomerulonephritis in pregnancy and shares with other immunologic diseases and kidney diseases a relationship with adverse maternal outcomes, whose entity and pattern is only partially quantified. Recent studies provide new information and a systematic review regarded progression of kidney disease. The discussion of the outcomes with respect to low-risk pregnancies may help to perfect the estimation of the risks, and to identify specific research needs. Methods: A search strategy was built on Medline, EMBASE and the Cochrane review for the period January 2000–April 2017, aimed at retrieving both case series (defined as with at least 6 pregnancies in women with IgA nephropathy) and case reports, to look into rare occurrences. All papers, with or without control groups, were selected if they reported on at least one pregnancy outcome, or on long-term kidney function. Search strategy, paper selection and data extraction were done in duplicate (PROSPERO N 42016042623). Meta-analysis of case series was performed with Metanalyst Beta 3.13. Case reports were analysed narratively. Results: The search retrieved 556 papers, of which 27 were included (13 series and 14 case-reports). The case series report on 581 women with 729 pregnancies. The analysis was performed in comparison to the available control groups: 562 non-pregnant controls were available for the analysis of progression of kidney disease. As for pregnancy related outcomes (preeclampsia (PE), pregnancy induced hypertension (PIH), preterm birth, small babies), we meta-analyzed the data with respect to the only series of low-risk pregnancies (1418 pregnancies). When compared with women who never got pregnant after diagnosis of IgA nephropathy, in the present meta-analysis pregnancy in women with IgA nephropathy was not associated with a higher risk of progression of kidney disease, possibly due to the overall preserved kidney function at baseline: end-stage kidney disease (OR 0.68; CI 0.28–1.65). Conversely, the incidence of adverse pregnancy-related outcomes was increased compared to low-risk controls: PE and PIH were more than ten-fold increased (OR 11.80; CI 7.53–18.48 and OR 10.39; CI 5.45–19.80), while the increase in risk of preterm birth and “low birth weight babies” was less marked (OR 3.37; CI 1.91–5.95 and OR 2.36; CI 1.52–3.66), a discrepancy suggesting the occurrence of “late” or “maternal” PE, that may affect less severely foetal growth or shorten gestation. In conclusion, in the present meta-analysis IgA nephropathy was not associated with an increased progression of kidney disease. The more than ten-fold increased risk of PIH and PE, in combination with a doubled risk of small babies, suggests the occurrence of “late” or “maternal” PE, usually less affecting early foetal growth. This finding may be of help in defining control policies, while further research is needed to guide clinical management.
Highlights
IgA nephropathy is probably the most common primary glomerular nephritis worldwide; its higher incidence in young people makes it highly relevant in pregnancy [1].The present term of IgA nephropathy encompasses two previously defined diseases, usually known by their eponyms: Berger’s disease, in which the IgA deposition is limited to the kidney, and Henoch-Shönlein, in which IgA nephropathy is a part of a systemic vasculitis that could involve the skin and the gastro-intestinal tract, with asymmetric acute osteoarthritis [2,3]
To try to further add to the knowledge in this important field, we considered several recent publications, not available at the time of the first review, and we focused a second systematic review on the effect of IgA nephropathy on pregnancy and of pregnancy on the progression of IgA nephropathy, on the new millennium, on the account of the changes in disease management and maternofetal care occurring over time, and we attempted for the first time a meta-analytical comparison with a low-risk population, in order to better quantify the risk of the various adverse pregnancy outcomes, as a further support for counseling
Our review may add information to a previous recent systematic review, which included papers published since the start of Medline, and was mainly focused on the progression of kidney disease in patients with IgA nephropathy with and without pregnancy [23]
Summary
IgA nephropathy is probably the most common primary glomerular nephritis worldwide; its higher incidence in young people makes it highly relevant in pregnancy [1].The present term of IgA nephropathy encompasses two previously defined diseases, usually known by their eponyms: Berger’s disease, in which the IgA deposition is limited to the kidney, and Henoch-Shönlein, in which IgA nephropathy is a part of a systemic vasculitis that could involve the skin and the gastro-intestinal tract, with asymmetric acute osteoarthritis [2,3]. This risk is not negligible over the entire life span as progression to ERSD is reported from rare to frequent, depending on morphological, clinical and laboratory characteristics, and treatment For these reasons, IgA nephropathy is usually considered as a disease that may remit, but that is never completely cured [14,15,16,17,18]. The more than ten-fold increased risk of PIH and PE, in combination with a doubled risk of small babies, suggests the occurrence of “late” or “maternal” PE, usually less affecting early foetal growth This finding may be of help in defining control policies, while further research is needed to guide clinical management
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