Background. Cyclosporine (CsA) therapy must often be continued during pregnancy to maintain maternal health in such conditions as organ transplantation and autoimmune disease. This meta-analysis was performed to determine whether CsA exposure during pregnancy is associated with an increased risk of congenital malformations, preterm delivery, or low birthweight. Methods. Various health science databases were searched to identify relevant articles. Articles selected for inclusion in the study were required to be free of any apparent selection bias and report outcomes in at least 10 newborns exposed to CsA in utero, specifically commenting on the presence or absence of congenital malformations. Article selection and data extraction were performed by two independent reviewers, with adjudication in cases of disagreement. To assess risks of CsA exposure, a summary odds ratio was calculated. Prevalence of malformations was calculated as a rate for all cyclosporine-exposed live births and for the subgroups identified. Ninety-five percent confidence intervals were constructed for both the odds ratio and prevalence rates. Results. Fifteen studies (6 with control groups of transplant without use of cyclosporine; total patients: 410) met the inclusion criteria for major malformations, 10 for preterm delivery (4 with control groups; total patients: 379) and 5 for low birth weight (1 with control groups; total number of patients: 314). The calculated odds ratio of 3.83 for malformations did not achieve statistical significance (CI 0.75‐19.6). The overall prevalence of major malformations in the study population (4.1%) also did not vary substantially from that reported in the general population. OR for prematurity [1.52 (CI 1.00 ‐2.32)] did not reach statistical significance although the overall prevalence rate was 56.3%. The OR for low birth weight [1.5 (CI 0.95‐ 2.44 based on 1 study)]. Conclusions. CsA does not appear to be a major human teratogen. It may be associated with increased rates of prematurity. More research is needed to evaluate whether cyclosporine increases teratogenic risk.

Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis.

Pregnancy has become one of the expected benefits afforded to women with successful organ transplants. This article discusses the most recent data about the effects on the mother and child of pregnancy in the recipients of solid-organ transplants.

/pdf/pregnancy-in-recipients-of-solid-organs-effects-on-mother-uc9wdx1l8h.pdf

Pregnancy in Recipients of Solid Organs — Effects on Mother and Child

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. 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. 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   35 years as compared to women aged 25–34 years. 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.

/pdf/pregnancy-outcomes-in-women-with-kidney-transplant-2fbscpugi6.pdf

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

Ideally, immunosuppressive drugs would not be necessary in pregnancy. However, in connective tissue disease (especially systemic lupus erythematosus, SLE) vasculitis, and sometimes antiphospholipid antibody syndrome, their use is necessary both to protect the health of the mother and to insure the success of the pregnancy. The more commonly used drugs will be reviewed, with an emphasis on human data, when available. Methotrexate and leflunamide will not be considered, for they should never be used in pregnancy.

Immunosuppressive drug use in pregnancy

Objective: To assess the current physical status and developmental outcome of children born to mothers following renal transplantation. Methodology: A cross-sectional prevalence survey of 48 children born to 34 women transplanted at a single centre from 1971 to 1992 was performed. Data on maternal renal disease, immunosuppression, pregnancy, delivery and child development were collected using hospital records and parental questionnaire. Children underwent physical examination, urinalysis and urinary tract ultrasound examination (US). Results: Maternal renal failure was due to reflux nephropathy/chronic pyelonephritis (16), chronic glomerulonephritis (eight) and other causes (10). All mothers received prednisolone immunosuppression, as sole therapy (one), as part of triple therapy (one). Sixteen (47%) received azathioprine/prednisolone and 16 (47%) cyclosporin/prednisolone. Twenty-three girls and 25 boys aged 9 months to 18 years were studied (median age 5.2 years); 27/48 (56%) were born prematurely, 21/48 (44%) with birthweight (BW) < 2500 g 21/48 (44%) were small for gestation (BW < 10th centile). General health and physical assessment were unremarkable in 45/48 (94%) and 41/43 (95%), respectively. Development was considered normal in 47/48 (98%). Four of 40(10%) had urinary tract abnormalities on US. Conclusions: Despite a high incidence of preterm delivery, low birth weight, intrauterine growth retardation and urinary tract abnormalities, the overall outcome for children of renal transplant recipient mothers is good.

Children of renal transplant recipient mothers

Many centers still recommend avoidance of pregnancy after renal transplantation because of fears for the safety of both mother and fetus. These fears are in part based on a lack of information concerning the effects of newer immunosuppressive drugs such as cyclosporine on the course and outcome of pregnancy. The present study examines the experience of first pregnancies following renal transplantation in a single center, with emphasis on the role of CsA. Data on the first pregnancies of 22 women transplanted between 1977 and 1988 were studied. The mean age of patients at the time of transplant was 23.4 +/- 3.1 years and interval from transplant to pregnancy was 34.5 +/- 24.5 months (range 1-75 months). Twelve patients received CsA alone or in combination with other immunosuppressives, while the remaining 10 patients received azathioprine and prednisone. Mean serum creatinine fell progressively during pregnancy in both CsA- and azathioprine-treated mothers. Mean CsA dose rose during pregnancy while mean CsA blood concentration fell during the 2nd trimester (P = 0.042). The gestation period ranged from 27 to 40 weeks (35.5 +/- 3.3) with 14 pregnancies ending prematurely prior to 37 weeks. Thirteen deliveries occurred by Caesarian section. Hypertension complicated 10 pregnancies. Birth weight correlated directly with both maternal weight gain (r = 0.57; P less than 0.02) and gestational age (r = 0.9; P less than 0.01). Ten of 23 offspring were below the 10th percentile for weight. Mean birth weight ranged from 0.72 to 3.7 kg (2.3 +/- 0.84 kg). The mean birth weight and gestational age of children born to mothers taking CsA were lower than those in azathioprine treated mothers but these differences were not statistically significant. Successful pregnancy is possible following renal transplantation, although there is a high rate of prematurity, low birth weight, and intrauterine growth retardation. CsA dose requirements may be increased. Maternal risks including hypertension require that such pregnancies be handled by a multidisciplinary team approach.

The outcome of pregnancy following renal transplantation--the experience of a single center.

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The outcome of pregnancy following renal transplantation--the experience of a single center.