The management and clinical outcomes of pregnancies in women with urea cycle disorders: A review of the literature and results of an international survey.

An increasing number of women with urea cycle disorders (UCDs) are reaching child-bearing age and becoming pregnant. Improved diagnostics and increased awareness of inherited metabolic diseases has also led to more previously undetected women being diagnosed with a UCD during or shortly after pregnancy. Pregnancy increases the risk of acute metabolic decompensation with hyperammonemia-which can occur in any trimester, and/or the postpartum period, and may lead to encephalopathy, psychosis, coma, and even death, if not diagnosed promptly and treated appropriately. There are also (theoretical) concerns that a maternal UCD, or its treatment, may cause potential risks for the unborn child. Currently evidence on management and outcome of pregnancies in UCDs is limited to case reports and there are no clear guidelines. In order to inform management and investigate outcomes of pregnancies in women with a UCD, we performed a retrospective review of published cases and analyzed data collected from an international online survey. We conclude that, although risk during the intra- and postpartum period exists, multidisciplinary management by an experienced team and a prospective plan usually result in successful pregnancy, labor, delivery, and postpartum period. No deaths were reported in mothers managed accordingly. With the exception of male neonates with Ornithine Transcarbamylase deficiency, the clinical outcome of children born to mothers with UCDs appears positive, although follow-up is limited. The outcome for women presenting with a first acute metabolic decompensation during pregnancy or postpartum is less favorable. Deaths were associated with diagnostic delay/late management of hyperammonemia in previously undiagnosed women.

Recurrent metabolic alkalosis following ketone body treatment of adult mitochondrial trifunctional protein deficiency: A case report.

Recent studies have reported the potential for the therapeutic use of ketones in the form of ketone salts (KSs) in pediatric patients with fatty acid oxidation disorders (FAODs). We report a case of ketone salt administration in an adult patient with mitochondrial trifunctional protein deficiency (MTPD), an ultra-rare inborn error of the fatty acid metabolism. This patient was treated with oral KSs during an episode of sepsis of unknown origin. Before KS supplementation was initiated, he had developed severe rhabdomyolysis as well as a respiratory insufficiency that did not respond to emergency treatment aimed at stabilizing the metabolic decompensation by promoting anabolism. Therefore, KS supplementation was attempted twice to support his energy production and help regain metabolic stability. In both instances, KS supplementation led to a considerable metabolic alkalosis, which prompted its discontinuation. This adverse event could have been caused by an increase in extracellular sodium load due to KS administration. Therefore, the clinical applicability of KSs in adults may be limited. Alternative chemical forms of beta-hydroxybutyrate (ßHB), such as ketone esters, might provide a more acceptable safety profile for future research into the therapeutic benefits of ketone body supplementation in adult patients with FAODs.

Antecolic versus retrocolic route of the gastroenteric anastomosis after pancreatoduodenectomy: a randomized controlled trial.

OBJECTIVE: To investigate the relationship between the route of gastroenteric (GE) reconstruction after pancreatoduodenectomy (PD) and the postoperative incidence of delayed gastric emptying (DGE). BACKGROUND: DGE is one of the most common complications after PD. Recent studies suggest that an antecolic route of the GE reconstruction leads to a lower incidence of DGE, compared to a retrocolic route. In a nonrandomized comparison within our trial center, we found no difference in DGE after antecolic or retrocolic GE reconstruction. METHODS: Ten middle- to high-volume centers participated in the patient inclusion. Patients scheduled for PD who gave written informed consent were included and randomized during surgery after resection. Standard operation was a pylorus-preserving PD. Primary endpoint was DGE. Secondary endpoints included other complications and length of hospital stay. RESULTS: There were 125 patients in the retrocolic group, and 121 patients in the antecolic group. Baseline and treatment characteristics did not differ between the study groups. In the retrocolic group, 45 patients (36%) developed clinically relevant DGE compared with 41 (34%) in the antecolic group (absolute risk difference: 2.1%; 95% confidence interval: -9.8% to 14.0%). There were no differences in need for postoperative (par)enteral nutritional support, other complications, hospital mortality, and median length of hospital stay. CONCLUSIONS: The route of GE reconstruction after PD does not influence the postoperative incidence of DGE or other complications. The etiology and treatment of DGE, which occurs frequently after both procedures, need further investigation. The GE reconstruction after PD should be routed according to the surgeon's preference.