Citations

AbstractBackgroundPregnancy after solid organ transplant is a significant priority for transplant recipients but how patients report being counseled is unknown.MethodsWe performed a single‐center retrospective cohort study and telephone survey of female patients ages 18–49 at the time of kidney, pancreas, or liver transplant from 2000 to 2012 (n = 532). Data on pregnancy counseling, fertility, and maternal, fetal‐ and transplant‐specific outcomes were collected. Multivariate Cox models assessed the impact of pregnancy on graft‐specific outcomes.ResultsThe survey response rate was 29% (n = 152). One‐third (n = 51) of women were actively counseled against pregnancy by one or more providers. A total of 17 pregnancies occurred among nine patients (5.9%), with 47% live births, 47% early embryonic demises, 5.9% stillbirths. Of live births, 50% were premature. Gestational complications, including diabetes, hypertension, and preeclampsia were present in 88% of mothers. Pregnancy after transplant was associated with higher rates of acute rejection than nulliparous transplant recipients (33% vs. 5.6%, p = 0.07) but did not significantly affect graft survival (HR = 1.00, 95% CI 0.99–1.01), after stratifying by organ and adjusting for clinical factors.ConclusionThis study suggests that transplant patients are being counseled against pregnancy despite acceptable risks of complications and no specific effects on long‐term graft function.

Background —Genetic defects are being increasingly recognized in the etiology of primary cardiomyopathy (CM). Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first step in the β-oxidation spiral of fatty acid metabolism, the crucial pathway for cardiac energy production. Methods and Results —We studied 37 patients with CM, nonketotic hypoglycemia and hepatic dysfunction, skeletal myopathy, or sudden death in infancy with hepatic steatosis, features suggestive of fatty acid oxidation disorders. Single-stranded conformational variance was used to screen genomic DNA. DNA sequencing and mutational analysis revealed 21 different mutations on the VLCAD gene in 18 patients. Of the mutations, 80% were associated with CM. Severe CM in infancy was recognized in most patients (67%) at presentation. Hepatic dysfunction was common (33%). RNA blot analysis and VLCAD enzyme assays showed a severe reduction in VLCAD mRNA in patients with frame-shift or splice-site mutations and absent or severe reduction in enzyme activity in all. Conclusions —Infantile CM is the most common clinical phenotype of VLCAD deficiency. Mutations in the human VLCAD gene are heterogeneous. Although mortality at presentation is high, both the metabolic disorder and cardiomyopathy are reversible.