Angiotensin-II Use for Refractory Hypotension in an Infant With Bilateral Renal Agenesis.

Infants with congenital bilateral renal agenesis are at significant risk for morbidity and mortality, despite substantial and continuing advances in fetal and neonatal therapeutics. Infants with bilateral renal agenesis may episodically develop severe hypotension that can be refractory to traditional vasopressors. Synthetic angiotensin-II has been successfully used in adult and a few pediatric patients with refractory hypotension but has not been extensively studied in infants. We describe the use of angiotensin-II in treating refractory hypotension in a premature infant with congenital bilateral renal agenesis admitted to the NICU. Within 48 hours, he no longer required other vasopressors. Subsequently, angiotensin-II was gradually weaned and discontinued over 10 days and the patient was ultimately discharged from the hospital. This case demonstrates that angiotensin-II may be a helpful agent to treat refractory hypotension in infants with bilateral renal agenesis.

Off-Label Use and Safety of Drug Use in Vascular Anomalies.

BACKGROUND: Off-label drug use is associated with an increased risk of adverse drug reactions. It is common in pediatrics and in rare diseases, which are two characteristics applying to vascular anomalies (VA). OBJECTIVES: The aim of this work was to quantify off-label drug use in VA and assess its safety. METHODS: A review was conducted to extract a list of drugs used in VA management. A drug was considered to have significant safety concerns if a black box warning was present or if a serious adverse drug reaction (SADR) was reported in at least 1% of the patients (SADR is defined as a noxious and unintended response to a drug that occurs at any dose and results in hospitalization, prolongation of existing hospitalization, congenital malformation, persistent or significant disability or incapacity, life-threatening condition, or death). The labelling status and safety of each drug was assessed based on the product monograph, Micromedex, and the FDA data. RESULTS: We found that 98.9% of the inventoried drugs were used off-label or unlicensed for VA management. Only the oral solution of propranolol hydrochloride (Hemangeol®) for the treatment of infantile hemangiomas is approved. Significant safety issues concerned 73% of the drugs and were more frequent among systemic than locally delivered drugs. CONCLUSIONS: Off-label drug use in VA is the rule and not the exception. Significant safety concerns are common. It is necessary to carefully weigh risk and benefits for every patient when using systemic and local treatments carrying safety concerns. Patients should be openly informed and involved in the decision-making process.

Live-Birth Outcomes and Congenital Malformations After Progestin-Primed Ovarian Stimulation in Maternal Endometriosis.

PURPOSE: In patients who had advanced endometriosis, we use different protocols including GnRH agonist, GnRH antagonist and progestin-primed ovarian stimulation (PPOS) protocols to assess live-birth congenital malformations delivered after in vitro fertilization (IVF) and vitrified embryo transfer cycles. METHODS: A retrospective cohort study is conducted by us. It includes 1495 live-born infants in maternal endometriosis. From January 2010 to January 2017, we brought into infants who underwent either gonadotropin-releasing hormone agonist long protocol, gonadotropin-releasing hormone antagonist protocol or PPOS. We chose neonatal outcomes and congenital malformations as our major measures. RESULTS: Neonatal outcomes, as well as congenital malformations, were considered as the main measures, and gestational age, birth weight, birth length, multiple births and early neonatal death are included. All groups were comparable. The GnRH antagonist group (1.41%) and the GnRH antagonist protocol group (1.8%) had the same incidence of live-birth defects as the PPOS groups (1.33%) were similar. There were no apparent differences when it came to congenital malformations among the three groups. Multivariate logistic regression showed that infertility-time factors as well as multiple births combined to add the risk of congenital malformations; the adjusted odds were 1.143 (95% confidence interval [CI]: 0.988-1.323) and 3.253 (95% CI: 1.359-7.788). Besides, no association was found among various ovarian stimulations as well as congenital birth defect programs, maternal age, body mass index, parity or infant sex. CONCLUSION: This study suggests that, in contrast to conventional ovarian stimulation, PPOS neither has any effect on neonatal outcomes in IVF adverse effects nor does it elevate the rate of congenital malformations in late endometriosis. However, randomized controlled trials of the long-term outcomes of children born after PPOS protocols for maternal endometriosis are needed and the follow-up studies were conducted to confirm this result.

Malformations congénitales oro-cervico-faciales au service d'odonto-stomatologie et chirurgie maxillo-faciale de l'hôpital national Donka

Les malformations congénitales cervico-oro-faciales sont des défauts structurels, fonctionnels, comportementaux et métaboliques qui se développent au cours de la période d'organogenèse de la sphère cervico-oro-faciale affectant la qualité de vie des patients. Le but de ce travail était de contribuer à l'étude des malformations congénitales cervico-oro-faciales. Il s'agit d'une étude descriptive menée dans le service d'odontostomatologie et de chirurgie maxillo­faciale de hôpital national Donka sur une période d'un mois incluant tous les patients présentant une malformation congénitale oro-cervico-faciale ayant fait l'objet d'un diagnostic, un traitement et un suivi post-thérapeutique. 28 cas de malformations congénitales cervico-oro-faciales ont été colligés soit une fréquence de 35,44 %. Les patients dont l'âge se situe entre 0 et 10 ans ont été les plus nombreux. Lesexratio était de 1,15 en faveur du sexe masculin. Conakry a été le plus grand pourvoyeur de patients avec un taux de 78,58 %. Et 25 % des patients avaient tenté auparavant un traitement ailleurs avant d'avoir consulté notre service. Les fentes labiales ont été les plus nombreuses soit 25 %. Dans notre série la plastie dont la Z-Plastie a été l'acte le plus réalisé. La totalité de nos patients ont été soumis à un traitement antalgique pendant les heures et jours qui ont suivi l'intervention. 98,70 % des cas ont été soumis à une antibiothérapie. La suite opératoire a été favorable dans 92,86 % des cas. Les malformations congénitales cervico-oro-faciales sont fréquentes, diverses et variées. Le diagnostic post-natal est aisé et précoce. Les fentes labiales ont représenté la forme nosologique la plus fréquente. Seule la chirurgie a été réalisée chez tous nos patients

Agenesis of the dorsal pancreas presenting with diabetic ketoacidosis - a case report and literature review.

BACKGROUND: Agenesis of the dorsal pancreas (ADP) is clinically rare, and it is usually accompanied by abdominal pain. Various disorders of glucose metabolism associating with ADP have been reported, but there are only two studies reporting a correlation between ADP and DKA in English literature. CASE PRESENTATION: We present a case of a patient with ADP accompanied by abdominal pain and diabetic ketoacidosis as the initial clinical presentation. A 30-year-old man presented with a 3-month history of recurrent onset of persistent mild epigastric pain, which worsen when eating. Laboratory tests revealed metabolic acidosis, hyperglycemia, and ketonuria. Phase contrast CT and MRCP showed the absence of the body and tail of the pancreas, as well as the dorsal pancreatic duct. The C-peptide release test indicated ß-cell dysfunction. A combination therapy of insulin, pancreatic enzyme supplements, and mosapride citrate were administrated and the pain gradually resolved. CONCLUSIONS: As glucose metabolism disorders can vary across different individuals, we advise clinicians to consider the diagnosis of ADP for a patient who presents with a glucose metabolism disorder accompanied by abdominal pain, pancreatitis or steatorrhea.

Neonatal outcomes and congenital malformations in children born after dydrogesterone application in progestin-primed ovarian stimulation protocol for IVF: a retrospective cohort study.

PURPOSE: Dydrogesterone (DYG) has been demonstrated to be an alternative progestin in the progestin-primed ovarian stimulation (PPOS) protocol with comparable oocyte retrieval and pregnancy outcomes. However, its safety regarding neonatal outcomes and congenital malformations is still unclear. PATIENTS AND METHODS: This retrospective cohort study included 3556 live-born infants after in vitro fertilization and vitrified embryo transfer cycles using the DYG + human menopausal gonadotropin (hMG) protocol (n=1429) or gonadotropin-releasing hormone (GnRH)-agonist short protocol (n=2127) from January 2014 to December 2017. Newborn information was gathered from standardized follow-up questionnaires and/or access to medical records within 7 days after birth. Associations between ovarian stimulation protocols and outcome measures were analyzed by binary logistic regression after adjusting for confounding factors. RESULTS: In both singletons and twins, birth characteristics regarding mode of delivery, newborn gender, gestational age, birthweight, length at birth and Z-scores were comparable between the two protocols. For adverse neonatal outcomes, the two protocols showed no significant differences on the rates of low birthweight, very low birthweight, preterm birth, very preterm birth, small-for-gestational age, large-for-gestational age and early neonatal death after adjustment. Furthermore, the incidence of major congenital malformations in the DYG + hMG protocol (1.12%) was similar to that in the GnRH-agonist short protocol (1.08%), with the adjusted odds ratio of 0.98 (95% confidence interval [CI]: 0.40-2.39) and 0.90 (95% CI: 0.33-2.41) in singletons and twins, respectively. CONCLUSION: Our data suggested that compared with the conventional GnRH-agonist short protocol, application of DYG in the PPOS protocol was a safe option for the newborn population without compromising neonatal outcomes or increasing congenital malformation risks.

A propensity-matched study of the association between optimal folic acid supplementation and birth defects in Shaanxi province, Northwestern China.

The association between folic acid supplementation and birth defects other than neural tube defects remains unclear. We utilized data from a large population-based survey to examine the association between folic acid supplementation and birth defects in Northwestern China. A total of 29,204 women with infants born between 2010 and 2013 were surveyed in Shaanxi province, Northwestern China, using a stratified multistage sampling method. Propensity scores were used to match 9,293 women with optimal folic acid supplementation with 9,293 women with nonoptimal folic acid supplementation, and the effects of optimal folic acid supplementation on birth defects were assessed by a conditional logistic regression model. After propensity score matching, the overall birth defect rate, cardiovascular system defect rate and nervous system defect rate for the women with optimal folic acid supplementation were lower than those for the women with nonoptimal folic acid supplementation (overall birth defects: OR = 0.71, 95% CI = 0.57-0.89, P = 0.003; cardiovascular system defects: OR = 0.65, 95% CI = 0.44-0.96, P = 0.032; nervous system defects: OR = 0.13, 95% CI = 0.02-0.99, P = 0.049). Optimal folic acid supplementation was associated with a decreased prevalence of birth defects, especially in the cardiovascular system and nervous system. Our findings have important implications for birth defect intervention with folic acid supplementation for countries with a high prevalence of birth defects, such as China.

Agenesis of dorsal pancreas in a young adult: a rare cause of diabetes mellitus.

Dorsal pancreatic agenesis is an extremely rare entity characterised by absence of body and tail of pancreas, while there are so many other developmental anomalies of the pancreas that have been reported. Here we report a 25-year-old young man who presented with pain in the abdomen, recurrent loose stools and hyperglycaemia. On radiological imaging study, there was complete agenesis of the dorsal pancreas except for thin stripe of tissue at the level of the uncinate process. Both exocrinedysfunction and endocrine dysfunction were present in this patient. Patient was supplemented with pancreatic enzyme preparation and insulin.

Intensive vaginal dilation using adjuvant treatments in women with Mayer-Rokitansky-Kuster-Hauser syndrome: retrospective cohort study.

AIMS: To evaluate the effect of adjuvants during intensive vaginal dilator therapy for functional and anatomical neovagina creation in women with Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH). METHODS: This retrospective cohort study included 75 women with MRKH undergoing intensive vaginal dilator treatment between 2000 and 2014. One specialist nurse performed non-surgical vaginal dilation aided by adjuvants, during inpatient admissions for several dilation sessions per day. Following discharge, women continued dilation at home and were advised to attend fortnightly follow-up appointments. RESULTS: Outcomes from 68 women were analysed. The median age of starting treatment was 18 years (range: 13-36). There was a mean of 3 days per admission (range 1-5) with a median of 10 dilation sessions per admission. Adjuvant treatment was used by 48/68 (71%) women: oestriol cream 29/68 (43%), 50:50 nitrous oxide and oxygen 44/68 (65%), diazepam 8/68 (12%), lidocaine ointment 26/68 (39%), paracetamol 35/68 (51%) and naproxen 2/68 (3%). There were no statistically significant differences for changes in vaginal parameters. Women receiving adjuvants had a median increase of 4.5 cm (0.5-7 cm) in neovaginal length compared with women not receiving adjuvants who had a median increase of 3.25 cm (0-7 cm) during intensive treatment. Women who received adjuvants tolerated more dilation sessions per day (10 vs 6.5 median sessions respectively) than those who did not (P < 0.001). Of those with documented length at discharge, 42/56 (75%) women had an anatomical neovagina of 7 cm or greater length. CONCLUSIONS: Vaginal dilation delivered by intensive treatment and supplemented by adjuvant treatments in a multi-disciplinary centre is a rapid and effective method for creation of a neovagina in women with MRKH.

Calcitriol reduces kidney development disorders in rats provoked by losartan administration during lactation.

Calcitriol has important effects on cellular differentiation and proliferation, as well as on the regulation of the renin gene. Disturbances in renal development can be observed in rats exposed to angiotensin II (AngII) antagonists during lactation period. The lack of tubular differentiation in losartan-treated rats can affect calcitriol uptake. This study evaluated the effect of calcitriol administration in renal development disturbances in rats provoked by losartan (AngII type 1 receptor antagonist) administration during lactation. Animals exposed to losartan presented higher albuminuria, systolic blood pressure, increased sodium and potassium fractional excretion, and decreased glomerular filtration rate compared to controls. These animals also showed a decreased glomerular area and a higher interstitial relative area from the renal cortex, with increased expression of fibronectin, alpha-SM-actin, vimentin, and p-JNK; and an increased number of macrophages, p-p38, PCNA and decreased cubilin expression. Increased urinary excretion of MCP-1 and TGF-ß was also observed. All these alterations were less intense in the losartan + calcitriol group.The animals treated with calcitriol showed an improvement in cellular differentiation, and in renal function and structure. This effect was associated with reduction of cell proliferation and inflammation.

Unusual association of Turner syndrome and Mayer-Rokitansky-Küster-Hauser syndrome.

Gonadal dysgenesis and Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) are the most common causes of primary amenorrhoea. Patients with gonadal dysgenesis present with primary amenorrhoea and lack of secondary sexual characteristics, which, in contrast, are present in patients with MRKHS. The coexistence of the 2 syndromes has been reported in only a few studies so far. We describe a case of a 15-year-old girl who presented with short stature and primary amenorrhoea. Investigations revealed hypergonadotropic hypogonadism, and absence of the uterus, and upper two-thirds of the vagina, with presence of the rudimentary lower third of the vagina and non-visualised bilateral ovaries on imaging. Karyotyping obtained by lymphocyte culture GTG banding revealed 45X/46XX. The patient was diagnosed as having a rare case of gonadal dysgenesis with MRKH. She was started on growth hormone therapy. The association of these syndromes is uncommon, and has further implications on fertility and pregnancy, affecting the quality of life.

50 years of the Hungarian Congenital Abnormality Registry.

The mandatory notification of patients ("cases") with different congenital abnormalities (CAs) diagnosed from birth until the end of the first postnatal year by medical doctors was ordered by the Ministry of Health in Hungary in 1962 and this CA-registry was continued as the Hungarian Congenital Abnormality Registry (HCAR) based on the international recommendation from 1970. The primary objective of the HCAR has been to determine the baseline birth prevalence rate of different CAs as reliably as possible, with three secondary objectives: (i) to detect temporal and/or spatial clusters of CAs; (ii) to evaluate increasing or decreasing time trends of CAs; and (iii) to assist in the planning of medical and social services for children and families affected by CA so that appropriate resources are allocated efficiently and effectively. This paper summarizes the activities and the evolution of the HCAR over the past 50 years (1962-2011) including the Hungarian Case-Control Surveillance of Congenital Abnormalities for postmarketing surveillance of drug teratogenicity and prevention of CAs; the special evaluation of unidentified multiple CAs; the Hungarian Surveillance of Germinal Mutations and several international collaborations. In conclusion, Hungary enjoyed optimal conditions for the HCAR due to a centralized state health system; all deliveries took place in inpatient clinics; the quality of pediatric care was high and pediatricians notified most CAs. Autopsy was mandatory in infant death, the staff of the HCAR did not consider this CA-registry only as a statistical system but the Hungarian Center for Congenital Anomaly Control and the Hungarian Case-Control Surveillance of Congenital Abnormalities based on the HCAR worked with close collaboration with the parents in order to promote the possible good quality of life of their affected children and to prevent their risk of recurrence.

The RASopathies.

The RASopathies are a clinically defined group of medical genetic syndromes caused by germline mutations in genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) pathway. These disorders include neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lentigines, capillary malformation-arteriovenous malformation syndrome, Costello syndrome, cardio-facio-cutaneous syndrome, and Legius syndrome. Because of the common underlying Ras/MAPK pathway dysregulation, the RASopathies exhibit numerous overlapping phenotypic features. The Ras/MAPK pathway plays an essential role in regulating the cell cycle and cellular growth, differentiation, and senescence, all of which are critical to normal development. Therefore, it is not surprising that Ras/MAPK pathway dysregulation has profound deleterious effects on both embryonic and later stages of development. The Ras/MAPK pathway has been well studied in cancer and is an attractive target for small-molecule inhibition to treat various malignancies. The use of these molecules to ameliorate developmental defects in the RASopathies is under consideration.

Corrección intrauterina de mielomeningocele: experiencia del programa de medicina y terapia fetal del Hospital Universitario Virgen del Rocío / Intrauterine myelomeningocele repair: Experience of the fetal medicine and therapy program of the Virgen de Rocío University Hospital

La forma más frecuente de espina bífida es el mielomeningocele, para el que no existe un tratamiento postnatal óptimo. Además del trastorno motor o sensitivo dependiente del nivel de la lesión, los niños suelen tener asociada la malformación de Arnold Chiari ii. El mielomeningocele presenta una alta mortalidad y puede acompañarse, hasta en el 80-90%, de hidrocefalia que es responsable de la gran afectación neurocognitiva, precisando de derivación para su supervivencia. La reparación intrauterina de malformaciones fetales mediante acceso abierto a través de histerotomía se ha convertido en una opción terapéutica gracias a la mejora de las técnicas quirúrgicas y anestésicas, y de la correspondiente instrumentación, que han convertido este tipo de intervenciones en una práctica relativamente frecuente. El tratamiento anestésico debe orientarse tanto a la madre como al feto, siendo importante mantener controlados los factores hemodinámicos que regulan el flujo placentario, la dinámica uterina, las pérdidas sanguíneas y el bienestar fetal. Dentro de nuestro Programa de Medicina y Terapia Fetal se han realizado 21 procedimientos de cirugía fetal abierta, 17 procedimientos EXIT y 4 procedimientos para la corrección intrauterina de mielomeningocele fetal. Describimos nuestra experiencia en la corrección intrauterina de mielomeningocele fetal mediante cirugía fetal abierta (AU)

The most frequent form of spina bifida is myelomeningocele. There is no optimal postnatal treatment for this defect. In addition to the motor or sensory deficits, which depend on the location of the lesion, the defect is usually associated with Chiari ii malformation in affected children. Myelomeningocele has high mortality and, in up to 80% to 90% of patients, can be accompanied by hydrocephalus, which causes severe neurocognitive impairment and requires the patient to be shunted for survival. Intrauterine repair of fetal malformations employing open access through hysterotomy has become a therapeutic option due to improved anesthetic and surgical techniques and instrumentation, which have allowed this type of intervention to become relatively frequent. Anesthetic treatment should focus on both the mother and fetus and the hemodynamic factors regulating placental flow, uterine dynamics, blood loss and fetal well-being must remain well-controlled. Within our Program for Fetal Medicine and Therapy, 21 open fetal interventions have been performed: 17 EXIT procedures and 4 procedures for the intrauterine correction of fetal myelomeningocele. We describe our experience of the intrauterine repair of fetal myelomeningocele through open fetal surgery (AU)

Endoscopic treatment of anterior glottic webs according to Lichtenberger technique and results on 18 patients.

Anterior glottic webs are most frequently acquired and result in a major vocal handicap. Many treatment modalities have been reported in the literature. None of them achieves perfect morphological or functional results. We present our series treated by an endoscopic technique based on CO(2) laser section of the web, mitomycin application and placement of a temporary silastic stent. We retrospectively reviewed the charts of 18 consecutive patients with anterior webs treated at our university hospital between 2003 and 2010. The endoscopic technique consisted of the section of the web with the CO(2) Acublade system, immediate application of mitomycin C and placement of a silastic stent. No tracheostomy was required. The stent was removed 3 weeks later. Patients had a vocal evaluation pre and postoperatively. It consisted of a video-stroboscopic examination, the global score of the Voice Handicap Index, the global and roughness scores of the perceptive voice evaluation according to Hirano, acoustic and aerodynamic parameters. Eighteen patients were included in the study with a mean age of 46 years (min. = 5, max. = 76). Twenty-two percent were women. All patients had postoperative speech therapy. The mean follow-up is 48.4 months (3-87 months). At the last follow-up, none of the patients had recurrence of the laryngeal web. The grade G of dysphonia significantly decreased from 2 to 1 (p = 0.035). CO(2) laser resection of anterior webs with mitomycin C application and placement of a silastic stent for 3 weeks induces a good morphological result with absence of web reformation but without substantial voice improvement observed in our series.

Concentrado de complejo protrombínico para el tratamiento de deficiencias congénitas o adquiridas en factores de coagulación / Concentrate of prothrombin complex for the treatment of congenital or acquired deficiencies in coagulation factors

INTRODUCCIÓN: Los FII, FVII, FIX y FX son denominados como factores de coagulación dependientes de vitamina K. La deficiencia adquirida de estos factores comúnmente ocurre durante el tratamiento de antagonistas de la vitamina K. Estas situaciones pueden ser revertidas por la suspensión del tratamiento con antagonistas de vitamina K, la administración de vitamina K o la administración de plasma fresco congelado (PFC). Sin embargo, en pacientes con hemorragia severa espontánea o inducida por traumatismo, o pacientes con riesgo de hemorragia que requieran una intervención de emergencia, la administración de concentrado de complejo protrombínico parece ser una opción más adecuada. La Hemofilia A (deficiencia de FVIII), B (deficiencia de FIX) y la enfermedad de von Willebrand (deficiencia de factor von Willebrand) representan la mayor parte los desórdenes de la coagulación congénitos. El tratamiento consiste básicamente en la reposición de los FVIII y FIX en dos modalidades: a demanda o preventivo. En Uruguay se encuentra incluido en el FTM únicamente el FVIII, el cual está indicado para el tratamiento y profilaxis de hemorragias en pacientes con hemofilia A (deficiencia congénita del factor VIII) y deficiencia adquirida del FVIII. Adicionalmente se encuentra disponible en el mercado nacional, pero no incluidos en el FTM el FVIIa, FVIII con factor de Willebrand y FIX. Octaplex® es un concentrado de complejo protrombínico (CCP) de administración intravenosa conteniendo como principios activos Factor II, Factor VII, Factor IX, Factor X, proteína C, proteína S y heparina.OBJETIVOS: Evaluar la eficacia y seguridad del concentrado de complejo protrombínico (CCP) para el tratamiento deficiencias congénitas o adquiridas en factores de coagulación. MÉTODOS: Se realizó una revisión sistemática de la evidencia clínica y posterior análisis de las principales variables de eficacia y seguridad. RESULTADOS: Los 2 principales estudios de Octaplex® incluyeron pacientes en tratamiento con anticoagulantes con hemorragia grave o que requerían de una intervención quirúrgica o de un procedimiento diagnóstico invasivo urgente. El estudio LEX-201 incluyó solamente 10 pacientes con hemofilia B o deficiencia del FVII, por lo que no fue considerado. Fueron identificados otros 10 estudios, los cuales evaluaron otras marcas comerciales con similar composición a Octaplex®. Esto hace que los resultados deban ser considerados con cautela, principalmente los de seguridad. Los ensayos fueron mayormente no controlados y con bajo número de pacientes, por lo que la calidad de la evidencia no es óptima. Los pacientes tratados con CCP (Octaplex®) presentaron una reducción del INR a partir de los 10 a 15 minutos post-infusión, al igual que un aumento en las concentraciones de los factores de coagulación. En cuanto a seguridad, el tratamiento con CCP principalmente puede producir transmisiones virales como hepatitis A u otros (4 de 80 pacientes) y aumento en la incidencia de eventos tromboembólicos. DISCUSIÓN: El producto Octaplex® es utilizado desde hace varios años en distintos países, sin embargo cuenta con una reducida evaluación clínica. En particular, no tiene ningún ensayo clínico finalizado comparando Octaplex® versus PFC. La falta de evidencia no permite conocer la eficacia y seguridad de Octaplex® en el tratamiento de deficiencias congénitas en factores de coagulación dependientes de vitamina K, siendo los ensayos mayormente en población con deficiencias adquiridas. CONCLUSIONES: La inclusión del CCP al FTM puede presentar beneficios clínicos en el tratamiento de pacientes que requieren de profilaxis, reposición perioperatoria y tratamiento de hemorragias graves con deficiencia adquirida de factores de coagulación del complejo protrombínico, cuando sea requerida una corrección rápida de la deficiencia. No hay suficiente evidencia clínica que permita recomendar la utilización de CCP en otras indicaciones. Previo a la toma de decisión, es necesario contar con un impacto presupuestal de la inclusión de este medicamento desde la perspectiva del sistema de salud.(AU)

Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus-associated birth defects.

OBJECTIVE: The purpose of this study was to examine the risk of birth defects in relation to diabetes mellitus and the lack of use of periconceptional vitamins or supplements that contain folic acid. STUDY DESIGN: The National Birth Defects Prevention Study (1997-2004) is a multicenter, population-based case-control study of birth defects (14,721 cases and 5437 control infants). Cases were categorized into 18 types of heart defects and 26 noncardiac birth defects. We estimated odds ratios for independent and joint effects of preexisting diabetes mellitus and a lack of periconceptional use of vitamins or supplements that contain folic acid. RESULTS: The pattern of odds ratios suggested an increased risk of defects that are associated with diabetes mellitus in the absence vs the presence of the periconceptional use of vitamins or supplements that contain folic acid. CONCLUSION: The lack of periconceptional use of vitamins or supplements that contain folic acid may be associated with an excess risk for birth defects due to diabetes mellitus.

Early use of probiotics is important therapy in infants with severe congenital anomaly.

BACKGROUND: Infants with severe congenital anomaly often need to undergo operation followed by antibiotic therapy. As a result they inevitably acquire abnormal intestinal microbiota, which cause severe infections such as necrotizing enterocolitis. Also, intestinal function deteriorates and their nutritional state is very poor. In order to prevent these situations probiotic therapy is proposed as an effective supporting treatment. Probiotic therapy were therefore applied to infants with severe congenital anomaly as early as possible to ascertain its efficacy. METHODS: As probiotics, two bacteria were used: Bifidobacterium breve Yakult and Lactobacillus casei Shirota. Probiotic therapy was used in four infants with severe congenital anomaly as early as possible after surgery. Their intestinal microbiota and physical growth were followed through the treatment course. RESULTS: Two patients suffered from meconium peritonitis with ileal atresia. One patient was born with complex anomalies (omphalocele, bladder exstrophy, myelomeningocele). The fourth patient suffered from complete urorectal septum malformation. The intestinal microbiota of these four patients was first induced to be probiotic dominant and finally changed to commensal anaerobe dominant that was similar to normal intestinal microbiota. Pathogenic bacteria were seldom detected. The patients' physical growth was excellent despite short bowel and pulmonary hypoplasia. CONCLUSION: Probiotic therapy was effective in inducing probiotic dominant intestinal microbiota and normal intestinal microbiota in infants with severe congenital anomalies. As a result their intestinal absorptive functions were activated and severe infections were completely prevented. All of the infants grew well despite their physical disadvantages.

O uso de drogas psicotrópicas na gestação / The use of psychotropic drugs during pregnancy

Os transtornos psiquiátricos durante a gravidez constituem uma situação complexa para o médico no momento da abordagem do tratamento. Os riscos para o concepto do uso de medicação psiquiátrica na gravidez incluem o surgimento de malformações, toxicidade neonatal e sequelas comportamentais. Além disso, deve-se levar em consideração também o risco, tanto para a mulher gestante como para o feto, de conduzir a gestação paralelamente a esses transtornos psiquiátricos sem tratamento algum. As evidências quanto às ações teratogênicas dos antidepressivos não são convincentes. Há, porém, a possibilidade de efeitos tóxicos sobre o feto, devendo ser evitado sempre que possível. Estudos de caso-controle relatam risco para lábio leporino ou fenda palatina em crianças expostas a benzodiazepínicos durante a gestação de 11:10.000 nascimentos, um aumento de 80 por cento em comparação com o risco de 6:10.000 na população geral. Os recém-nascidos expostos intraútero às drogas antipsicóticas podem desenvolver sinais de disfunção extrapiramidal, como tremores, reflexos tendinosos profundos hiperativos e irritabilidade. No ser humano, o lítio administrado durante a gravidez provoca uma taxa elevada de anormalidades congênitas, incluindo a doença de Ebstein. O objetivo deste trabalho é revisar os principais riscos para a mãe e o feto no tratamento de doenças psiquiátricas durante a gravidez.

Psychiatric disturbances during pregnancy are complex for the physician to manage when approaching a patient's treatment. Fetal risks with the use of psychiatric medications during pregnancy are malformations, newborn toxicity and behaviour problems. Moreover, we have to consider maternal and fetal risks during pregnancy with the use of these drugs conducting the pregnancy with psychiatric disorders without any treatment. Evidences about the teratogenic effects of antidepressants are not convincing. However, there is the possibility of toxic effects to the fetus and we have to avoid this whenever possible. Controlled studies suggest a risk of 11:10.000 births of cleft lip or palate in children exposed to benzodiazepines during pregnancy, an incidence 80 percent higher than the risk of 6:10.000 in the general population. Newborns exposed to intra-uterine antipsychotic drugs can develop signs of extrapyramidal dysfunction, like tremors, hyperactive reflexes and irritability. The use of lithium during pregnancy is related to high rates of congenital abnormalities, including Ebstein disease. The purpose of this article is to review the main maternal and fetal risks of treating psychiatric diseases during pregnancy.