Maternal and Fetal Outcomes in Pregnant Kidney Transplant Recipients

Due to disruption of hypothalamic gonadal axis, women with end-stage renal disease (ESRD) have impaired fertility, resulting in a very low incidence of conception in women on dialysis (range, 0.9% to 7%). In some cases, recipients of kidney transplantation experience a rapid restoration of fertility, making transplantation the optimal treatment for women with ESRD who wish to become pregnant.

There are challenges associated with pregnancy in a kidney transplant recipient, including the risk of adverse maternal complications of preeclampsia and hypertension, as well as the risk of adverse fetal outcomes of premature birth, low birth weight, and small for gestational age infants. There are also risks from the side effects of immunosuppression medication, and the risk of deterioration of allograft function. These risks call for preconception counseling, family planning, and contraception as part of the counseling process prior to transplantation.

There are limited data available on clinical outcomes of pregnancy in kidney transplant recipients. Silvi Shah, MD, and colleagues recently conducted a systematic review and meta-analysis to identify all studies of pregnancy-related outcomes in kidney transplant recipients worldwide and to estimate pooled incidence of pregnancy outcomes, maternal complications, and fetal complications. Secondary goals included examination of the impact of pregnancy on allograft loss and allograft rejection, identification of the ideal maternal age for conception, and determination of the ideal time of conception following kidney transplantation. Results of the analysis were reported online in BMC Nephrology [2019; doi.org/10.1186/s12882-019-1213-5].

The researchers searched PubMed/MEDLINE, Elsevier EMBASE, Scopus, BIOSIS Previews, ISI Science Citation Index Expanded, and the Cochrane Central Register of Controlled Trials from their earliest date of inception through August 31, 2017, as well as abstracts from the annual American Transplant Congress from January 1, 2013, through August 31, 2017. Key search terms used were pregnancy complications, pregnancy outcome, maternal outcome, fetal outcome, birth outcome, kidney transplant, or renal transplant.

Observational studies (prospective cohort, retrospective cohort, and cross-sectional), case series, and case reports (with n >10 pregnancies) that examined pregnancy, maternal outcomes, and fetal outcomes in women ≥18 years of age who received a kidney transplant were eligible for inclusion. Studies analyzing the teratogenic effects of mycophenolate or sirolimus, and non-English language studies were excluded.

The search yielded 4134 citations. Of those, the researchers reviewed 136 full-text articles, and selected 87 to be included in the final study cohort.  Three studies were from Africa, 31 from Asia, 31 from Europe, 10 from North America, four from Oceania, and eight from South America. The 87 studies represented 6712 pregnancies in 4174 kidney transplant recipients. Mean maternal age was 29.6 years and mean interval between kidney transplant and pregnancy was 3.7 years.

The outcomes included live birth rate (72.9%; 95% confidence interval [CI], 70.0-75.6), miscarriages rate (15.4%; 95% CI, 13.8-17.2), induced abortion rate (12.4%; 95% CI, 10.4-14.7), stillbirths rate (5.1%; 95% CI, 4.0-6.5), and rate of ectopic pregnancies (2.4%; 95% CI, 1.5-3.7).

Live birth rates were higher in the study cohort of kidney transplant recipients than in the general population in the United States (72.9% vs 62%); the rates were favorable across all geographic regions. Overall, the rate of miscarriage was slightly lower than in the US general population (15.4% vs 17.1%); it was higher across Africa (21.0%; 95% CI, 14.3-29.9) and South America (20.2%; 95% CI, 15.6-25.7).

The rate of induced abortion was also lower than in the general US population (12.4% vs 18.6%). South America had the highest rate of induced abortion (19.8%; 95% CI, 12.2-30.3), followed by Asia (13.3%; 95% CI, 9.6-18.3), Oceania (11.5%; 95% CI, 9.3-14.0), North America (10.9%; 95% CI, 5.9-19.2), Europe (10.0%; 95% CI, 7.3-13.5), and Africa (7.7%; 95% CI, 1.4-32.6). In the total cohort, the rate of stillbirth was higher than in the US general population (5.1% vs 0.6%). Stillbirth rate was highest in Asia (6.6%; 95% CI, 4.8-9.0), and lowest in Africa (2.6%; 95% CI, 0.4-16.5). The rate of ectopic pregnancy was slightly higher than in the general population in the United States (2.4% vs 1.4%); the highest rate was in Asia (3.3%; 95% CI, 1.1-9.8).

Results from subgroup analyses of studies published from 2000 to 2017 for pregnancy outcomes were consistent with the current findings.

In the overall cohort, the rate of preeclampsia was 25.1% (95% CI, 18.5-24.9; US mean, 3.8%), cesarean section, 62.6% (95% CI, 57.6-67.3; US mean, 31.9%), gestational diabetes, 5.7% (95% CI, 3.7-8.9; US mean, 9.2%), and pregnancy induced hypertension, 24.1% (95% CI, 18.1-31.5).

The rate of preterm birth (defined as babies born alive prior to 37 weeks of gestation) in the overall cohort was 43.1% (95% CI, 38.7-47.6) and the rate of neonatal mortality was 3.8% (95% CI, 2.8-5.2). The highest rates of preterm birth were in South America (55.0%) and the lowest were in North America (35.4%). Mean gestational age for newborns was 34.9 weeks (US mean, 38.7 weeks) and the mean birth weight was 2470 g (US mean, 3389 g). Compared with the US mean, neonatal mortality was high across all geographical regions; the highest rate was in Africa (18.4%) and the lowest was in North America (1.3%).

With the exception of neonatal mortality, results from the subgroup analyses for fetal outcomes were consistent with the present findings (the neonatal mortality rate was slightly lower in the subgroup analysis, 2.9% vs 3.8%).

Overall, the rate of acute graft rejection during pregnancy among 822 kidney transplant recipients was 9.4% (comparable to US mean of 9.1%). The highest rates of allograft failure were in Asia (11.0%); the lowest were in Africa (4.8%). Among 489 participants in 12 studies reporting 2-year post pregnancy graft loss, there were 32 cases of graft loss (9.2%).

The researchers cited the possibility of reporting bias, the inability to account for differences in socioeconomics and healthcare conditions, and the inability to assess pregnancy outcomes in relation to immunosuppression regimens as limitations to the findings.

“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,” the researchers said.

Takeaway Points

  1. Pregnancy in women who have received a kidney transplant presents clinical challenges due to the risk of adverse clinical outcomes.
  2. Results of a systematic review and meta-analysis found a favorable rate of live births in this patient population; however, the risks, both maternal and fetal, are high.
  3. These results can help healthcare providers with appropriate counseling and individualized management in transplant recipients considering pregnancy.