This study explores the effects of light maternal ethanol consumption during pregnancy on the appearance of minor malformations in neonates as well as on the contractile properties of their umbilical cord arteries (UCAs). Clinical external findings of newborns of women declaring light ethanol consumption during any period of their pregnancies [ethanol-exposed group (E group), n ϭ 79] were compared with those of nonexposed mothers [nonexposed to ethanol group (NE group), n ϭ 100]. Women who smoked or had any associated pathology were excluded. E group mothers consumed, on average, 200 -250 mL ethanol/trimester (upper limit 700 mL/ trimester). Sixty-six percent of the neonates in the E group presented at least one minor malformation (retromicrognathia and minor anomalies of the auricular/preauricular area were the more common), whereas only 16% of the NE group did (p ϭ 0.0000). The percentage of children exhibiting Apgar scores Ͻ7 was significantly greater in the E group (11% versus 2%, p ϭ 0.0119). UCAs from the E group developed significantly less contractile force (p Ͻ 0.05) than those of the NE group when exposed to 1 M serotonin (5-HT) or to a high K ϩ depolarizing solution. This difference persisted after inhibition of endothelial release of nitric oxide (NO) and prostacyclin. In conclusion, even light drinking should be considered a risk during pregnancy. (Pediatr Res 61: 456-461, 2007)

Risperidone is an antipsychotic commonly used during pregnancy. Because it can cross the placental barrier, our objective was to evaluate its actions on the smooth muscle of the human umbilical artery (HUA). Risperidone preincubation (1-300 nmol/L for 20 minutes) produced a significant decrease in maximum force development induced by serotonin or histamine in HUA rings. When applied on top of stable contractions induced by these agonists risperidone produced quick relaxations (IC(50) = 1 nmol/L for serotonin and 72 nmol/L for histamine). Risperidone induced the contraction of vascular rings depolarized by 40 mmol/L extracellular K(+) but not in the case of 80 mmol/L K(+), suggesting inhibition of K(+) channels. The patch-clamp technique showed that risperidone (3 nmol/L) inhibited whole-cell K(+) currents in freshly isolated HUA smooth muscle cells. Our results are the first showing risperidone effects in human vascular smooth muscle and highlight that its use during pregnancy should be adequately monitored.

No abstract

En la población pediátrica y particularmente en el ámbito de la psiquiatría infanto-juvenil, las indicaciones off-label representan una regla más que una excepción. Esta práctica puede ocurrir cuando un fármaco se indica en una patología, rango terapéutico, edad, vía de administración o duración distinta a las que se describen en el prospecto. Argentina, a diferencia de otros países, no tiene una regulación expresa en relación a la prescripción off-label. Por lo tanto, la indicación de un medicamento de manera diferente a la aprobada por la Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) no posee un marco normativo en lo referente a las condiciones que deben ser cumplidas al momento de ese acto médico. Si bien el uso off-label no se encuentra prohibido, conlleva un riesgo adicional. Con el objetivo de fomentar la investigación en pediatría, las agencias reguladoras como la Food and Drug Administration (FDA) y la European Medicines Agency (EMA) han introducido reformas legislativas. En el siguiente trabajo se revisarán las normativas vigentes de las agencias reguladores que competen a la población pediátrica y se analizarán criterios que orienten al médico al uso racional de la farmacoterapia off-label.