Maternal azathioprine therapy and depressed haemopoiesis in the babies of renal allograft patients

Abstract

Maternal immunosuppression with azathioprine during prcgnancy can depress fetal haemopoiesis resulting in neonatal thrombocytopenia and leucopenia with the potential for serious sequelae. The effect on the infant of adjusting azathioprine dosage on the basis of maternal total leucocyte count has been studied in 10 pregnancies in eight renal allograft recipients. Throughout the first six pregnancies azathioprine dosage was unchanged and although the characteristic pregnancy leucocytosis was evident it was not maintained in four patients whose leucocyte counts by 32 weeks gestation were significantly less than our norm [10-3 (SD 1.7) x1Oq/I] and who subsequently had babies with cord leucocyte counts G 8 . 0~ 10y/l, again significantly less than our norm [ 13.7 (SD 3.9) x 1O9/I]. A significant correlation existed hetwecn maternal leucocyte counts at 32 weeks gcstation and at delivery and cord leucocyte count (r=O.847; P<O41 and r=0.915: P<O.O1

In utero Exposure to Immunosuppressive Drugs

“…These neonates were clinically asymptomatic in 12/13 cases, but the immunomonitoring of children exposed to AZA is recommended [37]. Other reported adverse effects are decreased thymic shadow, anemia, reduced immunoglobulin levels, infections and septicemia, chromosomal abnormalities that may persist for up to 1 year, as well as sequelae from preterm delivery and IUGR [4,36].…”

“…AZA presents with teratogenicity in animal studies, with a high incidence of embryonic resorption and fetal anomalies [34,36]. However, it does not seem to be teratogenic in humans, even if there were isolated case reports of fetal malformations, including craniosynostosis, hypoplasia of the frontal lobe and ventriculomegaly [3].…”

Lupus Activity in Pregnancy

“…49 The level of 6-TGN is associated with myelosuppression in adults, and may rarely prompt transient myelosuppression after in utero exposure. 50 Series of pregnancies exposed to azathioprine for inflammatory bowel disease or renal transplants show no significant increase in fetal abnormalities. 47 Among renal transplant patients, however, up to 40% of the offspring were small for gestational age.…”

Medication Use in Pregnancy; Treating the Mother: Protecting the Unborn

“…Risks of other adverse pregnancy outcomes such as intrauterine growth retardation, prematurity (Goldstein et al 2007;Armenti et al 2002;Pirson et al 1985), and immunosuppression (Alter 1985;Davison et al 1985;DeWitte et al 1984;Sahasranaman et al 2008) have been reported, although these may be the results of the disease itself.…”