Long-Term Functional Outcomes of an Anorectal Malformation French National Cohort.

OBJECTIVES: The present study aimed to assess long-term functional outcomes of children with anorectal malformations (ARMs) across a network of expert centers in France. METHODS: Retrospective cross-sectional study of patients ages 6-30 years that had been surgically treated for ARM. Patient and ARM characteristics (eg, level, surgical approach) and functional outcomes were assessed in the different age groups. RESULTS: Among 367 patients, there were 155 females (42.2%) and 212 males (57.8%), 188 (51.2%) cases with, and 179 (48.8%) higher forms without, perineal fistula. Univariate and multivariate statistical analyses with logistic regression showed correlation between the level of the rectal blind pouch and voluntary bowel movements (odds ratio [OR] = 1.84 [1.31-2.57], P < 0.001), or soiling (OR = 1.72 [1.31-2.25], P < 0.001), which was also associated with the inability to discriminate between stool and gas (OR = 2.45 [1.28-4.67], P = 0.007) and the presence of constipation (OR = 2.97 [1.74-5.08], P < 0.001). Risk factors for constipation were sacral abnormalities [OR = 2.26 [1.23-4.25], P = 0.01) and surgical procedures without an abdominal approach (OR = 2.98 [1.29-6.87], P = 0.01). Only the holding of voluntary bowel movements and soiling rates improved with age. CONCLUSION: This cross-sectional study confirms a strong association between anatomical status and functional outcomes in patients surgically treated for ARM. It specifically highlights the need for long-term follow-up of all patients to help them with supportive care.

Vasodilator effects of dehydroepiandrosterone (DHEA) on fetal pulmonary circulation: An experimental study in pregnant sheep.

Persistent pulmonary hypertension (PPHN) remains a severe complication of the transition to extra-uterine life with significant morbidity and mortality in the newborns. Dehydroepiandrosterone (DHEA) represents a new pharmacological agent with vascular effects, including improvement of PPHN in several animal models. We hypothesized that DHEA could decrease pulmonary vascular resistance (PVR) in the pulmonary circulation of fetal sheep. We studied the effect of intravenous infusion of DHEA in fetal lambs using chronically instrumented sheep at 128 days of gestation. PVR was computed before and after intravenous infusion of increasing doses of DHEA. We assessed pre-treatment by L-nitroarginine, an inhibitor of NO production. Blood gases and doses of DHEA were measured in both sheep and fetus before/after DHEA infusion. Intravenous infusion of DHEA had a vasodilator effect with a significant decrease in PVR (respectively -11%, -14% and -36% after infusion of 6, 12 and 24 mg DHEA, p<0.01) without damaging effects on systemic circulation or on blood gases. The inhibitory effect of pre-treatment with L-nitroarginine resulted in a significant increase in PVR. We demonstrated a potent vasodilator effect of DHEA on fetal pulmonary circulation without deleterious effects. DHEA might represent a new treatment for PPHN.

Effects of n-3 polyunsaturated fatty acids in the fetal pulmonary circulation.

OBJECTIVE: Although evidence exists that n-3 polyunsaturated fatty acids may improve the outcome in patients with severe respiratory failure, little is known regarding their pulmonary circulatory effects. This question is clinically relevant in respiratory failure associated with pulmonary hypertension, in particular in newborn infants with persistent pulmonary hypertension. The objective of this study was to investigate the effects of n-3 polyunsaturated fatty acids on the fetal pulmonary circulation. DESIGN: Randomized, placebo-controlled comparative laboratory investigation. SETTING: University research facility. SUBJECTS: Fifty-two chronically prepared lamb fetuses. INTERVENTIONS: Catheters and ultrasonic flow transducer were placed through a left thoracotomy in the lamb fetus to determine aortic, pulmonary, and left atrial pressures and left pulmonary artery blood flow. MEASUREMENTS AND MAIN RESULTS: We compared the pulmonary vascular responses to 120 mins of Omegaven (lipid emulsions enriched in n-3 polyunsaturated fatty acids) or Intralipide (lipid emulsions enriched in n-6 polyunsaturated fatty acids) infusion. Then we investigated the effects of Omegaven on the pulmonary circulation after nitric oxide synthase inhibition by L-nitro-arginine, potassium channel blockade by tetraethylammonium, and cytochrome P450 epoxygenase inhibition by (methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Pulmonary artery and aortic pressures as well as blood gases and plasma lactate concentrations did not change during either fat emulsion infusion. Left pulmonary blood flow increased by 30% and pulmonary vascular resistance decreased by 28% during Omegaven infusion, whereas left pulmonary blood flow and pulmonary vascular resistance did not change during Intralipide infusion. This pulmonary vascular response to Omegaven was not altered by l-nitro-arginine. At the opposite, Omegaven induced pulmonary vasodilatation was abolished by tetraethylammonium and markedly attenuated by (methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. CONCLUSIONS: Lipid emulsion containing n-3 polyunsaturated fatty acids may induce a potent and sustained vasodilatation in the fetal lung. This pulmonary vasodilator response is mediated through production of vasoactive mediators by cytochrome P450 epoxygenase and through activation of potassium channels.