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      Pregnancy outcomes in women with kidney transplant: Metaanalysis and systematic review

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          Abstract

          Background

          Reproductive function in women with end stage renal disease generally improves after kidney transplant. However, pregnancy remains challenging due to the risk of adverse clinical outcomes.

          Methods

          We searched PubMed/MEDLINE, Elsevier EMBASE, Scopus, BIOSIS Previews, ISI Science Citation Index Expanded, and the Cochrane Central Register of Controlled Trials from date of inception through August 2017 for studies reporting pregnancy with kidney transplant.

          Results

          Of 1343 unique studies, 87 met inclusion criteria, representing 6712 pregnancies in 4174 kidney transplant recipients. Mean maternal age was 29.6 ± 2.4 years. The live-birth rate was 72.9% (95% CI, 70.0–75.6). The rate of other pregnancy outcomes was as follows: induced abortions (12.4%; 95% CI, 10.4–14.7), miscarriages (15.4%; 95% CI, 13.8–17.2), stillbirths (5.1%; 95% CI, 4.0–6.5), ectopic pregnancies (2.4%; 95% CI, 1.5–3.7), preeclampsia (21.5%; 95% CI, 18.5–24.9), gestational diabetes (5.7%; 95% CI, 3.7–8.9), pregnancy induced hypertension (24.1%; 95% CI, 18.1–31.5), cesarean section (62.6, 95% CI 57.6–67.3), and preterm delivery was 43.1% (95% CI, 38.7–47.6). Mean gestational age was 34.9 weeks, and mean birth weight was 2470 g. The 2–3-year interval following kidney transplant had higher neonatal mortality, and lower rates of live births as compared to > 3 year, and < 2-year interval. The rate of spontaneous abortion was higher in women with mean maternal age < 25 years and > 35 years as compared to women aged 25–34 years.

          Conclusion

          Although the outcome of live births is favorable, the risks of maternal and fetal complications are high in kidney transplant recipients and should be considered in patient counseling and clinical decision making.

          Electronic supplementary material

          The online version of this article (10.1186/s12882-019-1213-5) contains supplementary material, which is available to authorized users.

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          Most cited references97

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          Reproduction and transplantation: report on the AST Consensus Conference on Reproductive Issues and Transplantation.

          It has been almost 50 years since the first child was born to a female transplant recipient. Since that time pregnancy has become common after transplantation, but physicians have been left to rely on case reports, small series and data from voluntary registries to guide the care of their patients. Many uncertainties exist including the risks that pregnancy presents to the graft, the patient herself, and the long-term risks to the fetus. It is also unclear how to best modify immunosuppressive agents or treat rejection during pregnancy, especially in light of newer agents available where pregnancy safety has not been established. To begin to address uncertainties and define clinical practice guidelines for the transplant physician and obstetrical caregivers, a consensus conference was held in Bethesda, Md. The conferees summarized both what is known and important gaps in our knowledge. They also identified key areas of agreement, and posed a number of critical questions, the resolution of which is necessary in order to establish evidence-based guidelines. The manuscript summarizes the deliberations and conclusions of the conference as well as specific recommendations based on current knowledge in the field.
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            Pregnancy outcomes in solid organ transplant recipients with exposure to mycophenolate mofetil or sirolimus.

            Animal and limited human studies have raised concerns as to the safety of in utero exposure to mycophenolate mofetil (MMF) and sirolimus (SRL) in transplant recipients. This study examined the outcomes of pregnancies with exposure to MMF or SRL from 30 female transplant recipients (39 pregnancies) who have reported pregnancies to the National Transplantation Pregnancy Registry. Data were collected via questionnaires, phone interviews and medical records. There were 18 kidney recipients reporting 26 pregnancies with exposure to MMF: 15 livebirths (LB), 11 spontaneous abortions (SA). Structural malformations were reported in four of the 15 children (26.7%) including: hypoplastic nails and shortened fifth fingers (one), microtia with cleft lip and palate (one), microtia alone (one), and neonatal death with multiple malformations (one). One kidney/pancreas (K/P) recipient reported one SA. Three liver recipients reported three pregnancies; two LB (no malformations), and one second trimester SA. Two heart recipients reported one LB (no malformations) and two SA. SRL exposures included seven recipients (four kidney, one K/P and two liver) reporting four LB (one infant whose mother was switched from MMF to SRL during late pregnancy had cleft lip and palate and microtia) and three SA. A higher incidence of structural malformations was seen with MMF exposures during pregnancy compared to the overall kidney transplant recipient offspring, while no structural defects have as yet been reported with early pregnancy sirolimus exposures. Centers are encouraged to report all pregnancy exposures in transplant recipients.
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              Trends in birth weight and gestational length among singleton term births in the United States: 1990-2005.

              To estimate changes over time in birth weight for gestational age and in gestational length among term singleton neonates born from 1990 to 2005. We used data from the U.S. National Center for Health Statistics for 36,827,828 singleton neonates born at 37-41 weeks of gestation, 1990-2005. We examined trends in birth weight, birth weight for gestational age, large and small for gestational age, and gestational length in the overall population and in a low-risk subgroup defined by maternal age, race or ethnicity, education, marital status, smoking, gestational weight gain, delivery route, and obstetric care characteristics. In 2005, compared with 1990, we observed decreases in birth weight (-52 g in the overall population, -79 g in a homogenous low-risk subgroup) and large for gestational age birth (-1.4% overall, -2.2% in the homogenous subgroup) that were steeper after 1999 and persisted in regression analyses adjusted for maternal and neonate characteristics, gestational length, cesarean delivery, and induction of labor. Decreases in mean gestational length (-0.34 weeks overall) were similar regardless of route of delivery or induction of labor. Recent decreases in fetal growth among U.S., term, singleton neonates were not explained by trends in maternal and neonatal characteristics, changes in obstetric practices, or concurrent decreases in gestational length. III.
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                Author and article information

                Contributors
                513-558-0688 , silvishah2108@gmail.com
                lalgudrn@mail.uc.edu
                gupta2a4@mail.uc.edu
                sanghamk@mail.uc.edu
                welgeja@ucmail.uc.edu
                johansra@ucmail.uc.edu
                keaney@ucmail.uc.edu
                kaurtt@ucmail.uc.edu
                anuguptadr@gmail.com
                joffritm@ucmail.uc.edu
                Prasoon.Verma@cchmc.org
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                23 January 2019
                23 January 2019
                2019
                : 20
                : 24
                Affiliations
                [1 ]ISNI 0000 0001 2179 9593, GRID grid.24827.3b, Division of Nephrology Kidney C.A.R.E. Program, , University of Cincinnati, ; 231 Albert Sabin Way, MSB 6112, Cincinnati, OH 45267 USA
                [2 ]ISNI 0000 0001 2179 9593, GRID grid.24827.3b, Department of Environmental Health, , University of Cincinnati, ; Cincinnati, OH USA
                [3 ]ISNI 0000 0001 2179 9593, GRID grid.24827.3b, Health Sciences Library, , College of Medicine, University of Cincinnati, ; Cincinnati, OH USA
                [4 ]ISNI 0000 0004 0452 6114, GRID grid.413121.4, Buffalo Medical Group, ; Buffalo, NY USA
                [5 ]ISNI 0000 0000 9025 8099, GRID grid.239573.9, Division of Neonatology, , Cincinnati Children’s Hospital and Medical Center, ; Cincinnati, OH USA
                Author information
                http://orcid.org/0000-0002-9941-9404
                Article
                1213
                10.1186/s12882-019-1213-5
                6345071
                30674290
                fa84e3e9-2cc5-440f-a444-6590cb4f094d
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 30 September 2018
                : 15 January 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Nephrology
                pregnancy,kidney transplant,maternal,fetal,outcomes
                Nephrology
                pregnancy, kidney transplant, maternal, fetal, outcomes

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