Participants without children after transplantation
Of the 330 participants who never had a child, 105 (32%, 95% CI [27–37]) declared that they did not want to conceive after transplantation, 6 (2%, 95% CI [0.7–4]) male KT recipients were concerned about the risk of transmission of polycystic kidney disease (PKD), whereas 55 (17%, 95% CI [13–21]) suffered from infertility (Table 1). Childless participants seemed to be younger than the ones who had fathered children before KT only, with a median age of 50 years [IQR 39–59] and 59 years [IQR 53–64] respectively (Table 1).
Table 1
Description of participants without children
Covariate
|
Childless patients
(n = 330)
|
Age, median (IQR), years
|
50 (39–59)
|
Year of first transplantation, median (IQR)
|
2009 (2005–2012)
|
Reason, n (%, [95% CI])
|
|
No desire to father a child
|
105 (32%, [27–37])
|
Infertility
|
55 (17%, [13–21])
|
Erectile dysfunction
|
5 (1%, [0.5-4])
|
Spermatogenesis disorders
|
33 (10%, [7–14])
|
Other
|
17 (5%, [3–8])
|
Anxiety
|
37 (11%, [8–15])
|
Other
|
|
Age
|
7 (2%, [1–4])
|
Celibacy
|
75 (23%, [18–28])
|
Genetic PKD
|
6 (2%, [0.7-4])
|
Genetic disease other than PKD
|
11 (3%, [2–6])
|
Intellectual disability
|
4 (1%, [0.3-3])
|
Partner's infertility
|
3 (1%, [0.2-3])
|
Missing
|
27 (8%, [5–12])
|
Ongoing pregnancy, n (%, [95% CI])
|
4 (1%, [0.3-3])
|
IQR: interquartile range; PKD: polycystic kidney disease |
Outcome of pregnancies fathered by male kidney transplant recipients under immunosuppressive therapy at the time of conception
There were 349 children from 404 pregnancies fathered by 232 male KT recipients, including twin pregnancies. Unwanted outcomes occurred in the 404 pregnancies as follows: 37 (9%, 95% CI [7–12]) spontaneous abortions, 12 (3%, 95% CI [2–5]) therapeutic abortions, and 2 (0.5%, 95% CI [0.1–1]) still births. There were 10 (2%, 95% CI [1–5]) ongoing pregnancies at the time of the survey. Of the 349 living births, the median gestational age was 41 weeks (IQR [39–41]), with only 30 (9%, 95% CI [6–12]) pre-term deliveries. The median birth weight was 3.4 Kg (IQR [3–3.7]). There were 13 (4%, 95% CI [2–6]) congenital malformations reported (Table 2).
Table 2
Description and outcomes of pregnancies fathered by male kidney transplant patients
Covariate
|
All pregnancies
n = 404
|
First pregnancy
n = 245
|
Second pregnancy
n = 115
|
Third pregnancy
n = 35
|
Fourth pregnancy
n = 9
|
Age, median (IQR), years
|
41 (36–48)
|
41 (36–48)
|
42 (37–48)
|
43 (37.5–49)
|
48 (44–52)
|
Age at conception, median (IQR), years
|
34 (30–37)
|
33 (21–36)
|
35 (31–39)
|
37 (34–40)
|
41 (40–44)
|
Year of first transplantation, median (IQR)
|
2006 (1999–2010)
|
2006 (1999–2010)
|
2006 (1996–2008)
|
2005 (1994–2007)
|
1994 (1986–2002)
|
Transplant to conception time in years, median (IQR)
|
5 (2–8)
|
4 (1.5-7)
|
7 (4–10)
|
8 (6–11)
|
16 (13–19)
|
Immunosuppressive co-medication at the time of conception§
|
|
|
|
|
|
Corticosteroids
|
298 (74%, [69–78])
|
176 (72%, [66–77])
|
84 (73%, [64–81])
|
29 (83%, [66–93])
|
9 (100%, [66–100])
|
Azathioprine
|
59 (15%, [11–18])
|
44 (18%, [13–23])
|
13 (11%, [6–19])
|
1 (3%, [0.7–15])
|
1 (11%, [0.3–50])
|
MMF/MPA
|
313 (77%, [73–81])
|
190 (78%, [72–83])
|
92 (80%, [72–87])
|
26 (74%, [57–88])
|
5 (56%, [21–86])
|
Tacrolimus
|
255 (63%, [58–68])
|
156 (64%, [57–70])
|
70 (61%, [51–70])
|
22 (63%, [45–79])
|
7 (78%, [40–97])
|
Cyclosporine
|
152 (38%, [33–43])
|
94 (38%, [32–45])
|
43 (37%, [29–47])
|
13 (37%, [21–55])
|
2 (22%, [3–60])
|
Everolimus
|
5 (1%, [0.5-3])
|
3 (1%, [0.3-4])
|
2 (2%, [0.2-6])
|
0 (0%, [0–10])
|
0 (0%, [0–33])
|
Sirolimus
|
7 (2%, [1–4])
|
5 (2%, [0.7-5])
|
2 (2%, [0.2-6])
|
0 (0%, [0–10])
|
0 (0%, [0–33])
|
Belatacept
|
6 (1%, [0.5-3])
|
4 (2%, [0.4-4])
|
1 (1%, [0.1-5])
|
1 (3%, [0.7–15])
|
0 (0%, [0–33])
|
Other§§
|
40 (10%, [7–13])
|
18 (7%, [4–11])
|
16 (14%, [8–22])
|
5 (14%, [5–30])
|
1 (11%, [0.3–50])
|
Rejection episode before or during pregnancy
|
80 (20%, [16–24])
|
40 (16%, [12–22])
|
29 (25%, [18–34])
|
8 (23%, [10–40])
|
3 (33%, [7–70])
|
Pregnancy outcomes
|
|
|
|
|
|
Live births, including 6 twin pregnancies
|
349 (86%, [83–90])
|
222 (91%, [86–94])
|
94 (82%, [73–88])
|
26 (74%, [57–88])
|
7 (78%, [40–97])
|
Twin pregnancy
|
7 (2%, [0.5-3])
|
5 (2%, [0.7-5])
|
1 (1%, [0.1-5])*
|
1 (3%, [0.7–15])
|
0 (0%, [0–33])
|
Spontaneous abortion
|
37 (9%, [7–12])
|
18 (7%, [4–11])
|
14 (12%, [7–20])
|
4 (11%, [3–27])
|
1 (11%, [0.3–50])
|
Therapeutic abortion
|
12 (3%, [2–5])
|
6 (2%, [0.9-5])
|
2 (2%, [0.2-6])
|
3 (9%, [2–23])
|
1 (11%, [0.3–50])
|
Still births
|
2 (0.5%, [0.1-1])
|
0 (0%, [0-0.1])
|
0 (0%, [0–3])
|
2 (6%, [1–19])
|
0 (0%, [0–33])
|
Ongoing pregnancy
|
10 (2%, [1–5])
|
4 (2%, [0.4-4])
|
5 (4%, [1–10])
|
1 (3%, [0.7–15])
|
0 (0%, [0–33])
|
Live births, including twin pregnancies
|
349
|
222
|
94
|
26
|
7
|
Gestational age in weeks, median (IQR)
|
41 (39–41)
|
41 (38–41)
|
41 (39–41)
|
41 (39–41)
|
41 (39–41)
|
Pre-term delivery (< 37 weeks)
|
30 (9%, [6–12])
|
23 (10%, [7–15])
|
5 (5%, [2–12])
|
2 (8%, [1–25])
|
0 (0%, [0–41])
|
Birthweight (Kg), median (IQR)
|
3.4 (3-3.7)
|
3.3 (3-3.7)
|
3.4 (3-3.8)
|
3.5 (3-3.6)
|
3.5 (3.2–3.8)
|
Low birthweight (< 2.5 Kg)
|
20 (6%, [4–9])
|
16 (7%, [4–11])
|
3 (3%, [1–9])
|
1 (4%, [0.1–20])
|
0 (0%, [0–41])
|
Sex (male)
|
193 (55%, [50–61])
|
127 (57%, [50–64])
|
47 (50%, [40–60])
|
16 (62%, [41–80])
|
3 (43%, [10–82])
|
Intellectual disability
|
3 (1%, [0.2-3])
|
3 (1%, [0.3-4])
|
0 (0%, [0–4])
|
0 (%, [0–13])
|
0 (0%, [0–41])
|
Congenital malformation
|
13 (4%, [2–6])
|
10 (5%, [2–8])
|
3 (3%, [1–9])
|
0 (%, [0–13])
|
0 (0%, [0–41])
|
Values are presented as numbers and percentages [95% CI] unless otherwise specified. |
IQR: interquartile range; MMF/MPA: mycophenolate mofetil/mycophenolic acid; Kg: Kilograms |
§ Immunosuppressive agents of the father at the time of conception, more than one co-medication possible |
§§ Other: Immunosuppression including one of the following treatments before or at the time of conception: Cyclophosphamide, Intravenous immunoglobulin, Plasma exchange, Rituximab |
* The twin pregnancy was still ongoing at the time of the study |
The outcomes of pregnancies fathered by male KT recipients according to the father’s immunosuppressive medication at the time of conception are described in Tables 3.1 and 3.2. The immunosuppressive agents and the malformations or therapeutic abortions are displayed in Table 4. Since before the pregnancies the male patients were exposed to co-medication, outcomes can be declared in several columns. Of the 5 pregnancies within the partnerships of the participants treated by everolimus, there was one therapeutic abortion due to multiple malformations. The proportion of therapeutic abortions and malformations according to the immunosuppressive agents taken by the father were: 6 of 59 (10%, 95% CI [4–21]) pregnancies for azathioprine (AZA), 18 of 255 (7%, 95% CI [4–11]) pregnancies for tacrolimus, 19 of 298 (6%, 95% CI [4–10]) pregnancies for corticosteroid (CTC), 17 of 313 (5%, 95% CI [3–9]) pregnancies for MMF/MPA, and 6 of 152 (4%, 95% CI [1–8]) pregnancies for cyclosporine. The most common treatment associations were: CTC – MMF/MPA – tacrolimus (159 pregnancies conceived by 103 patients) and CTC – MMF/MPA – cyclosporine (72 pregnancies conceived by 45 patients), with a malformation rate of 3.7% (95% CI [1.5–8]) and 1.4% (95% CI [0.7–8.5]) respectively.
Table 3.1.
Description and outcomes of pregnancies fathered after kidney transplantation according to the fathers’ immunosuppressive medication at the time of conception
Covariate
|
MMF/MPA n=313
|
CTC n=298
|
Tacrolimus n=255
|
Cyclosporine n=152
|
Number of recipients
|
195
|
177
|
166
|
94
|
Age, median (IQR), years
|
40 (36-45)
|
43 (37-50)
|
40 (35-45)
|
46 (38-52)
|
Age at conception, median (IQR), years
|
34 (30-38)
|
34 (31-38)
|
35 (31-38)
|
33 (29-37)
|
Transplant to conception time§, median (IQR)
|
5 (2-9)
|
5 (3-10)
|
5 (7-10)
|
4 (2-7.5)
|
Pregnancy outcomes
|
|
|
|
|
Live births, including 6 twin pregnancies
|
268 (86%, [81-89])
|
257 (86%, [82-90])
|
219 (86%, [81-90])
|
136 (89%, [83-94])
|
Twin pregnancy
|
6 (2%, [0.7-4])*
|
6 (2%, [0.7-4])*
|
5 (2%, [0.6-5])
|
2 (1%, [0.2-5])*
|
Spontaneous abortion
|
32 (10%, [7-14])
|
29 (10%, [7-14])
|
23 (9%, [6-13])
|
12 (8%, [4-13])
|
Therapeutic abortion
|
8 (3%, [1-5])
|
10 (3%, [2-6])
|
8 (3%, [1-6])
|
2 (1%, [0.2-5])
|
Still births
|
2 (1%, [0.1-2])**
|
2 (0.7%, [0.1-2])**
|
2 (0.8%, [0-3])**
|
0 (0%, [0-2])
|
Ongoing pregnancy
|
8 (3%, [1-5])
|
5 (2%, [0.5-4])
|
8 (3%, [1-6])
|
3 (2%, [0.4-6])
|
Live births, including twins
|
268
|
257
|
219
|
136
|
Gestational age in weeks, median (IQR)
|
41 (39-41)
|
41 (39-41)
|
41 (39-41)
|
41 (39-41)
|
Pre-term delivery (<37 weeks)
|
24 (9%, [6-13])
|
22 (9%, [5-13])
|
16 (7%, [4-12])
|
16 (12%, [7-18])
|
Birthweight (Kg), median (IQR)
|
3.3 (3-3.7)
|
3.4 (3-3.7)
|
3.4 (3-3.7)
|
3.3 (2.9-3.7)
|
Low birthweight (<2.5 Kg)
|
18 (7%, [4-10])
|
10 (4%, [2-7])
|
12 (5%, [3-9])
|
9 (7%, [3-12])
|
Sex (male)
|
142 (53%, [47-59])
|
143 (56%, [49-62])
|
119 (54%, [47-61])
|
76 (56%, [47-64])
|
Intellectual disability
|
1 (0.4%, [0-2])
|
2 (0.8%, [0-3])
|
1 (0.5%, [0-3])
|
1 (0.7%, [0-4])
|
Congenital malformation
|
9 (3%, [1-6])
|
9 (4%, [2-7])
|
10 (5%, [2-8])
|
4 (3%, [1-7])
|
Values are presented as numbers and percentages [95% CI] unless otherwise specified.
As before the pregnancies the male patients were exposed to co-medication, one outcome can be declared in several columns.
MMF: Mycophelonate mofetil; CTC: corticosteroid; IQR: interquartile range
§ Transplant to conception time, in years
* One of the twin pregnancy was still ongoing at the time of the study
** In both stillbirths, from a twin pregnancy, a pulmonary malformation was discovered
Table 3.2.
Description and outcomes of pregnancies fathered after kidney transplantation according to the fathers’ immunosuppressive medication at the time of conception
Covariate
|
Azathioprine n=59
|
Sirolimus n=7*
|
Belatacept n=6*
|
Everolimus n=5*
|
Number of recipients
|
46
|
7
|
4
|
5
|
Age, median (IQR), years
|
51 (44-56)
|
40 (38-48)
|
39 (35-42)
|
55 (37-62)
|
Age at conception, median (IQR), years
|
34 (29-36)
|
34 (29-36)
|
38 (35-39)
|
37 (34-40)
|
Transplant to conception time§, median (IQR)
|
5 (2-9.5)
|
4 (1.5-12)
|
6 (5-8)
|
7 (4-10.8)
|
Pregnancy outcomes
|
|
|
|
|
Live births, including 6 twin pregnancies
|
55 (93%, [84-98])
|
5
|
4
|
5
|
Twin pregnancy
|
1 (2%, [0-9])
|
0
|
0
|
1
|
Spontaneous abortion
|
2 (3%, [0.5-11])
|
2
|
2
|
0
|
Therapeutic abortion
|
2 (3%, [0.5-11])
|
0
|
0
|
1
|
Still births
|
0 (0%, [0-6])
|
0
|
0
|
0
|
Ongoing pregnancy
|
1 (2%, [0-9])
|
0
|
0
|
0
|
Live births, including twins
|
55
|
5
|
4
|
5
|
Gestational age in weeks, median (IQR)
|
41 (39-41)
|
39 (38-40)
|
38 (38-39)
|
39 (36-41)
|
Pre-term delivery (<37 weeks)
|
5 (9%, [3-20])
|
0
|
0
|
2
|
Birthweight (Kg), median (IQR)
|
3.5 (3.1-3.6)
|
3 (2.4-3.3)
|
3.1 (2.9-3.2)
|
3.2 (2.9-3.6)
|
Low birthweight (<2.5 Kg)
|
1 (2%, [0.1-10])
|
1
|
0
|
0
|
Sex (male)
|
33 (60%, [46-73])
|
3
|
2
|
3
|
Intellectual disability
|
2 (4%, [0.5-13])
|
0
|
0
|
0
|
Congenital malformation
|
4 (7%, [2-17])
|
0
|
0
|
0
|
Values are presented as numbers and percentages [95% CI] unless otherwise specified.
As before the pregnancies the male patients were exposed to co-medication, one outcome can be declared in several columns.
MMF: Mycophelonate mofetil; IQR: interquartile range
§ Transplant to conception time, in years
* Due to the small number of events, percentages are not presented
Table 4
List of therapeutic abortions and congenital malformations identified among 25 offspring of male kidney transplant recipients exposed to immunosuppressive medication
Therapeutic abortion, n = 12
|
Year of pregnancy
|
Year of transplant
|
Paternal age*
|
Medical reason for abortion
|
Male KT recipients’ medication regimen at the time of conception
|
1986
|
1981
|
NA
|
Genetic disorder
|
AZA, prednisone
|
NA
|
1994
|
NA
|
Trisomy 21
|
MMF/MPA, tacrolimus, prednisone
|
2005
|
1979
|
31
|
Spina bifida and Arnold Chiari
|
AZA, prednisone
|
2012
|
2006
|
48
|
Ectopic pregnancy
|
MMF/MPA, cyclosporine
|
2013
|
2007
|
34
|
Trisomy 21
|
MMF/MPA, cyclosporine
|
2014
|
2010
|
36
|
missing
|
MMF/MPA, tacrolimus, prednisone
|
2015
|
2006
|
34
|
missing
|
MMF/MPA, tacrolimus, prednisone
|
2016
|
2009
|
40
|
missing
|
MMF/MPA, tacrolimus, prednisone
|
2016
|
2008
|
35
|
missing
|
Tacrolimus, prednisone
|
2016
|
2011
|
35
|
Multiple malformations
|
Tacrolimus, everolimus, prednisone
|
2018
|
2014
|
33
|
missing
|
MMF/MPA, tacrolimus, prednisone
|
2018
|
2013
|
43
|
missing
|
MMF/MPA, tacrolimus, prednisone
|
Congenital malformation, n = 13
|
Year of birth
|
Year of transplant
|
Paternal age*
|
Congenital malformation
|
Male KT recipients’ medication regimen at the time of conception
|
1998
|
1996
|
33
|
Cleft lip and palate
|
AZA, cyclosporine
|
2000
|
NA
|
NA
|
Deafness
|
AZA, cyclosporine, prednisone
|
2001
|
1998
|
32
|
Congenital phimosis
|
MMF/MPA, cyclosporine, tacrolimus, prednisone
|
2001
|
2000
|
NA
|
Cleft lip and palate
|
AZA, tacrolimus, prednisone
|
2002
|
1989
|
41
|
Complex cardio-facial syndrome
|
AZA, tacrolimus, prednisone
|
2005
|
2004
|
34
|
Left thumb's agenesis
|
MMF/MPA, tacrolimus, prednisone
|
2006
|
1992
|
25
|
Pyloric stenosis
|
MMF/MPA, tacrolimus, prednisone
|
2009
|
2007
|
21
|
Renal hypoplasia
|
MMF/MPA, tacrolimus
|
2012
|
2007
|
30
|
Hypospadias
|
MMF/MPA, cyclosporine
|
2015
|
2011
|
26
|
Hypoplastic toes
|
MMF/MPA, tacrolimus, prednisone
|
2015
|
2013
|
32
|
Urinary tract malformation
|
MMF/MPA, tacrolimus
|
2016
|
2010
|
32
|
Plagiocephaly
|
MMF/MPA, tacrolimus, prednisone
|
2017
|
2006
|
38
|
Wolff Parkinson White syndrome
|
MMF/MPA, tacrolimus, prednisone
|
MMF/MPA: Mycophelonate mofetil/Mycophenolic acid; AZA: Azathioprine |
* Age at conception of the pregnancy, in years |