Pregnancy outcomes after kidney graft in Italy: are the changes over time the result of different therapies or of different policies? A nationwide survey (1978-2013).
Kidney transplantation is the treatment of choice to restore fertility to women on renal replacement therapy. Over time, immunosuppressive, support therapies and approaches towards high-risk pregnancies have changed. The aim of this study was to analyse maternal-foetal outcomes in two cohorts of transplanted women who delivered a live-born baby in Italy in 1978-2013, dichotomized into delivery before and after January 2000.



A survey involving all the Italian transplant centres was carried out, gathering data on all pregnancies recorded since the start of activity at each centre; the estimated nationwide coverage was 75%. Data on cause of ESRD, dialysis, living/cadaveric transplantation, drug therapy, comorbidity, and the main maternal-foetal outcomes were recorded and reviewed. Data were compared with a low-risk cohort of pregnancies from two large Italian centres (2000-14; Torino and Cagliari Observational Study cohort).



The database consists of 222 pregnancies with live-born babies after transplantation (83 before 2000 and 139 in 2000-13; 68 and 121 with baseline and birth data, respectively), and 1418 low-risk controls. The age of the patients significantly increased over time (1978-99: age 30.7 ± 3.7 versus 34.1 ± 3.7 in 2000-13; P < 0.001). Azathioprine, steroids and cyclosporine A were the main drugs employed in the first time period, while tacrolimus emerged in the second. The prevalence of early preterm babies increased from 13.4% in the first to 27.1% in the second period (P = 0.049), while late-preterm babies non-significantly decreased (38.8 versus 33.1%), thus leaving the prevalence of all preterm babies almost unchanged (52.2 and 60.2%; P = 0.372). Babies below the 5th percentile decreased over time (22.2 versus 9.6%; P = 0.036). In spite of high prematurity rates, no neonatal deaths occurred after 2000. The results in kidney transplant patients are significantly different from controls both considering all cases [preterm delivery: 57.3 versus 6.3%; early preterm: 22.2 versus 0.9%; small for gestational age (SGA): 14 versus 4.5%; P < 0.001] and considering only transplant patients with normal kidney function [preterm delivery: 35 versus 6.3%; early preterm: 10 versus 0.9%; SGA: 23.7 versus 4.5% (P < 0.001); risks increase across CKD stages]. Kidney function remained stable in most of the patients up to 6 months after delivery. Multiple regression analysis performed on the transplant cohort highlights a higher risk of preterm delivery in later CKD stages, an increase in preterm delivery and a decrease in SGA across periods.



Pregnancy after transplantation has a higher risk of adverse outcomes compared with the general population. Over time, the incidence of SGA babies decreased while the incidence of 'early preterm' babies increased. Although acknowledging the differences in therapy (cyclosporine versus tacrolimus) and in maternal age (significantly increased), the decrease in SGA and the increase in prematurity may be explained by an obstetric policy favouring earlier delivery against the risk of foetal growth restriction.
Department of Clinical and Biological Sciences, University of Torino, Torino, Italy.|Nephrologie, CH du Mans, 72000 Le Mans France.
Giorgina Barbara
GB
Piccoli
UOC Nefrologia, Azienda Ospedaliera Brotzu, Cagliari, Italy.
Gianfranca
G
Cabiddu
SCDU Obstetrics Department of Surgical Sciences, Città della Salute e della Scienza, University of Torino, Torino, Italy.
Rossella
R
Attini
SCDU Obstetrics Department of Surgical Sciences, Città della Salute e della Scienza, University of Torino, Torino, Italy.
Martina
M
Gerbino
U.O. Nefrologia Dialisi e Trapianto, Dipartimento delle Insufficienze d'organo e dei trapianti, Policlinico S. Orsola Bologna, Bologna, Italy.
Paola
P
Todeschini
SC Nefrologia, AO Niguarda Ca' Granda, Milano, Italy.
Maria Luisa
ML
Perrino
Renal Transplantation Center 'A.Vercellone', Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, Città della Salute e della Scienza, University of Torino, Torino, Italy.
Ana Maria
AM
Manzione
UOC Nefrologia, Azienda Ospedaliera Brotzu, Cagliari, Italy.
Gian Benedetto
GB
Piredda
UO Nefrologia Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
Elisa
E
Gnappi
UOC Nefrologia 2, Dialisi e Trapianto, ARNAS Civico Palermo, Palermo, Italy.
Flavia
F
Caputo
U.O.C. Nefrologia e Dialisi, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
Giuseppe
G
Montagnino
Divisione di Nefrologia, Dialisi e Trapianto, Azienda Ospedaliera Universitaria 'San Giovanni di Dio e Ruggi d'Aragona', Salerno, Italy.
Vincenzo
V
Bellizzi
UOC Nefrologia e Dialisi, Ospedale San Martino, Belluno, Italy.
Pierluigi
P
Di Loreto
Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, Vicenza, Italy.
Francesca
F
Martino
SOC di Nefrologia, Dialisi e Trapianto Renale, Azienda Ospedaliero-Universitaria 'S. Maria della Misericordia' Udine, Udine, Italy.
Domenico
D
Montanaro
Department of Nephrology, Azienda Ospedaliero-Universitaria Policlinico Bari, Bari, Italy.
Michele
M
Rossini
Nephrology and Dialysis, Taormina Hospital, Taormina, Italy.
Santina
S
Castellino
SCDU Obstetrics Department of Surgical Sciences, Città della Salute e della Scienza, University of Torino, Torino, Italy.
Marilisa
M
Biolcati
SCDU Obstetrics Department of Surgical Sciences, Città della Salute e della Scienza, University of Torino, Torino, Italy.
Federica
F
Fassio
UOC Nefrologia, Azienda Ospedaliera Brotzu, Cagliari, Italy.
Valentina
V
Loi
SCDU Obstetrics Department of Surgical Sciences, Città della Salute e della Scienza, University of Torino, Torino, Italy.
Silvia
S
Parisi
SSD Epidemiology, Department of Clinical and Biological Sciences, AOU san Luigi, University of Torino, Italy.
Elisabetta
E
Versino
UOC Nefrologia, Azienda Ospedaliera Brotzu, Cagliari, Italy.
Antonello
A
Pani
SCDU Obstetrics Department of Surgical Sciences, Città della Salute e della Scienza, University of Torino, Torino, Italy.
Tullia
T
Todros
D000328:Adult; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007231:Infant, Newborn; D007558:Italy / Q000453:epidemiology; D016030:Kidney Transplantation; D011247:Pregnancy; D011248:Pregnancy Complications; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000453:epidemiology*; D012042:Registries; D011795:Surveys and Questionnaires
D007166:Immunosuppressive Agents