There are special implications of parenthood by immunosuppressed graft recipients. One which probably applies to both paternity and maternity is the possibility that the agents used to prevent rejection may contribute to fetal defects. At our institution, the studies by Githens and Rosenkrantz and their associa tes
11,12 showed that a high incidence of skeletal and central nervous system anomalies could be produced by giving large doses (4 to 30 mg/kg of body weight) of azathioprine to female mice during early pregnancy. Because this agent causes chromosome aberrations,
13 it might be assumed that sperm could be affected and that males under treatment could, therefore, also contribute to fetal abnormalities, even though Rosenkrantz et al could not confirm the hypothesis.
12 By the same logic, it would be reasonable to suspect an adverse role of adrenocortical steroids, since they lead in animal experiments to fetal anomalies
14 by unknown mechanisms.
In spite of the formidable theoretical reasons to fear complications of parenthood, there is now enough evidence to indicate that the risks are not exorbitant, particularly for paternity. In our own experience with 19 pregnancies brought to term by wives of male transplantation patients, there has been only one anomalous offspring. That child is the one described in a report of a case by Tallent et al.
10 The authors quite properly speculated about the role of the transplantation setting in the etiology of the complication. However, to place this case in a more realistic perspective, it is important to realize that it was the only such example in the Colorado series of male parents from which it was culled, and that, as such, it represented an incidence of 5.3%.
In the six live-born infants of female renal homograft recipients, there was also an example of a congenital anomaly; this was a pulmonary valve stenosis that required surgical correction at four months. Although the other five babies did not have such structural defects, this did not assure newborn vigor or even viability, since there was one death in the group. It is of interest that the infant that died was premature and was delivered from the woman with the worst homograft. Prematurity is not uncommon with nontransplantation patients with poor renal function.
15 However, in the offspring of other mothers with good renal function, there were examples of babies that were small or subject to respiratory complications. These unfavorable conditions have been seen in infants whose mothers have been receiving steroid therapy.
16In addition, two of the six infants had a complication to which both azathioprine and prednisone probably contributed. Neonatally, the babies had few peripheral lymphocytes, and in the one case in which an x-ray film of the chest was obtained, the thymic shadow could not be seen. In addition, there was both clinical and laboratory evidence of adrenocortical insufficiency. Fortunately, the features of this syndrome regressed spontaneously within a few days. However, failure to take the proper therapeutic measures might have resulted in death.
Thus far, in this comment, attention has been confined to the infant risk. There is probably also a higher-than-normal hazard to prospective mothers whose good health is dependent upon continuing function of their transplants. Conceivably, the heterotopic location of the homograft could be responsible for mechanical dystocia, but only under conditions that have not yet been encountered. With the standard technique for renal transplantation, the kidney is placed in the iliac fossa
7 outside the true pelvis, where it should not interfere with delivery. However, in some instances the homograft may lie within the birth canal, in which case special precautions would be necessary. This dangerous state could be identified with pyelograms.
It may be conceded that maternal morbidity is slight from mechanical injury to the homograft. The same may not be true for other kinds of homograft deterioration. Moore and Hume
3 and Caplan et al
6 recorded cases in which homograft function became impaired during late gestation and did not recover afterward. It could be argued that the renal damage in these patients was the consequence of coincidental chronic rejection, transmission glomerulonephritis, or other factors having nothing to do with the pregnancy. In our own observations, this explanation did not seem to pertain. There were three women who had worsening of function during pregnancy with return of function to the preexisting state after termination of pregnancy, suggesting that the gestational process was in some way responsible for the initial adverse changes.
In caring for a large number of long-term survivors after renal homotransplantation, we are often asked to provide opinions about the advisability of having children. On the basis of the studies of both males and females described in the present communication, some practical guidelines have evolved. Men are told that the prospects of having normal children are excellent and that the major consideration should be that their own long-term prognosis and consequent prospects of raising the offspring are still not known. Women are told approximately the same thing concerning the problems of anomalies and of their own life expectancy. However, it is also emphasized that risks in neonatal life are greater to the child and that, furthermore, there may be a slight intrinsic hazard to the homograft during gestation.
The publisher's final edited version of this article is available at 
