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      Risk of Preeclampsia and Adverse Pregnancy Outcomes after Heterologous Egg Donation: Hypothesizing a Role for Kidney Function and Comorbidity

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          Abstract

          Background and objectives: Preeclampsia (PE) is a risk factor for kidney diseases; egg-donation (ED) increasingly used for overcoming fertility reduction, is a risk factor for PE. CKD is also a risk factor for PE. However, kidney function is not routinely assessed in ED pregnancies. Objective of the study is seeking to assess the importance of kidney function and maternal comorbidity in ED pregnancies. Design, setting, participants and measurements. Design: retrospective observational study from clinical charts. Setting: Sant’Anna Hospital, Turin, Italy (over 7000 deliveries per year). Selection: cases: 296 singleton pregnancies from ED (gestation > 24 weeks), who delivered January 2008–February 2019. Controls were selected from the TOrino Cagliari Observational Study (1407 low-risk singleton pregnancies 2009–2016). Measurements: Standard descriptive analysis. Logistic multiple regression analysis tested: PE; pregnancy-induced hypertension; preterm delivery; small for gestational age; explicatory variables: age; BMI; parity; comorbidity (kidney diseases; immunologic diseases; thyroid diseases; other). Delivery over time was analyzed according to Kaplan Meier; ROC (Relative Operating Characteristic) curves were tested for PE and pre-term delivery, employing serum creatinine and e-GFR as continuous variables. The analysis was performed with SPSS v.14.0 and MedCalc v.18. Results: In keeping with ED indications, maternal age was high (44 years). Comorbidity was common: at least one potential comorbid factor was found in about 40% of the cases (kidney disease: 3.7%, immunologic 6.4%, thyroid disease 18.9%, other-including hypertension, previous neoplasia and all other relevant diseases—10.8%). No difference in age, parity and BMI is observed in ED women with and without comorbidity. Patients with baseline renal disease or “other” comorbidity had a higher risk of developing PE or preterm delivery after ED. PE was recorded in 23% vs. 9%, OR: 2.513 (CI 1.066–5.923; p = 0.039); preterm delivery: 30.2% vs. 14%, OR 2.565 (CI: 1.198–5.488; p = 0.044). Limiting the analysis to 124 cases (41.9%) with available serum creatinine measurement, higher serum creatinine (dichotomised at the median: 0.67 mg/dL) was correlated with risk of PE (multivariate OR 17.277 (CI: 5.125–58.238)) and preterm delivery (multivariate OR 2.545 (CI: 1.100–5.892). Conclusions: Within the limits of a retrospective analysis, this study suggests that the risk of PE after ED is modulated by comorbidity. While the cause effect relationship is difficult to ascertain, the relationship between serum creatinine and outcomes suggests that more attention is needed to baseline kidney function and comorbidity.

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          Preeclampsia and the risk of end-stage renal disease.

          It is unknown whether preeclampsia is a risk marker for subsequent end-stage renal disease (ESRD). We linked data from the Medical Birth Registry of Norway, which contains data on all births in Norway since 1967, with data from the Norwegian Renal Registry, which contains data on all patients receiving a diagnosis of end-stage renal disease (ESRD) since 1980, to assess the association between preeclampsia in one or more pregnancies and the subsequent development of ESRD. The study population consisted of women who had had a first singleton birth between 1967 and 1991; we included data from up to three pregnancies. ESRD developed in 477 of 570,433 women a mean (+/-SD) of 17+/-9 years after the first pregnancy (overall rate, 3.7 per 100,000 women per year). Among women who had been pregnant one or more times, preeclampsia during the first pregnancy was associated with a relative risk of ESRD of 4.7 (95% confidence interval [CI], 3.6 to 6.1). Among women who had been pregnant two or more times, preeclampsia during the first pregnancy was associated with a relative risk of ESRD of 3.2 (95% CI, 2.2 to 4.9), preeclampsia during the second pregnancy with a relative risk of 6.7 (95% CI, 4.3 to 10.6), and preeclampsia during both pregnancies with a relative risk of 6.4 (95% CI, 3.0 to 13.5). Among women who had been pregnant three or more times, preeclampsia during one pregnancy was associated with a relative risk of ESRD of 6.3 (95% CI, 4.1 to 9.9), and preeclampsia during two or three pregnancies was associated with a relative risk of 15.5 (95% CI, 7.8 to 30.8). Having a low-birth-weight or preterm infant increased the relative risk of ESRD. The results were similar after adjustment for possible confounders and after exclusion of women who had kidney disease, rheumatic disease, essential hypertension, or diabetes mellitus before pregnancy. Although the absolute risk of ESRD in women who have had preeclampsia is low, preeclampsia is a marker for an increased risk of subsequent ESRD. 2008 Massachusetts Medical Society
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            Risk of Adverse Pregnancy Outcomes in Women with CKD.

            CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; "general" combined outcome (preterm delivery, NICU, SGA); and "severe" combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4-5: "general" combined outcome, 34.1% versus 90.0%; "severe" combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a "baseline risk" for adverse pregnancy-related outcomes linked to CKD.
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              A Systematic Review and Meta-Analysis of Outcomes of Pregnancy in CKD and CKD Outcomes in Pregnancy.

              We undertook a systematic review and meta-analysis of published cohort studies and case-control studies to estimate (1) the risk of pregnancy complications among patients with CKD versus those without CKD and (2) the risk of CKD progression among pregnant patients versus nonpregnant controls with CKD.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                28 October 2019
                November 2019
                : 8
                : 11
                : 1806
                Affiliations
                [1 ]Obstetrics, Department of Surgery, University of Torino, Torino 10100, Italy; federica.fassio@ 123456hotmail.it (F.F.); rossella.attini@ 123456gmail.com (R.A.); alberto.revelli@ 123456unito.it (A.R.); gianluca.gennarelli@ 123456unito.it (G.G.); isabella.gazzani@ 123456hotmail.com (I.B.G.); emuccinelli@ 123456cittadellasalute.to.it (E.M.); cplazzotta@ 123456cittadellasalute.to.it (C.P.); guido.menato@ 123456unito.it (G.M.)
                [2 ]Nephrology, Centre Hospitalier Le Mans, Le Mans 72000, France; antoine.chatrenet@ 123456gmail.com
                [3 ]Laboratory of Statistics, University of Angers, Angers 49035, France; patrick.saulnier@ 123456chu-angers.fr
                [4 ]Nephrology, Brotzu Hospital, Cagliari 09134, Italy; gianfranca.cabiddu@ 123456tin.it
                [5 ]Department of Clinical and Biological Sciences, University of Torino, Torino 10100, Italy
                Author notes
                [* ]Correspondence: gbpiccoli@ 123456yahoo.it ; Tel.: +33-669-733-371
                [†]

                These authors contributed equally to this study.

                [‡]

                These authors contributed equally to this study.

                Author information
                https://orcid.org/0000-0002-8650-583X
                https://orcid.org/0000-0001-5243-0940
                https://orcid.org/0000-0003-1145-7404
                https://orcid.org/0000-0002-5797-3722
                https://orcid.org/0000-0003-3019-1090
                https://orcid.org/0000-0002-2632-4009
                Article
                jcm-08-01806
                10.3390/jcm8111806
                6912476
                31661864
                9821d8bc-2a9b-49b1-91d5-abdb7bd60fea
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 October 2019
                : 22 October 2019
                Categories
                Article

                pregnancy,egg donation,preterm delivery,preeclampsia,kidney function

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