Fármacos antiepilépticos usados en el embarazo y sus consecuencias sobre los resultados fetales: una revisión de la literatura / Antiepileptic drugs used in pregnancy and their consequences on fetal outcomes: a review of the literature

Los riesgos teratogénicos ocasionados por la exposición intrauterina a fármacos antiepilépticos (FAE) son conocidos, por lo que su prescripción se mantiene bajo estricto control. Describir los efectos adversos fetales de la exposición a FAE durante la gestación, reportados en la literatura durante el período 2016-2022. Revisión sistematizada de estudios que reportaron los efectos adversos fetales inducidos por la exposición a FAE en mujeres embarazadas en tratamiento por diagnósticos neurológicos, principalmente de epilepsia. La búsqueda se realizó en PubMed, Cochrane, Web of Science, SCOPUS, Biblioteca Virtual en Salud, Lilacs y SciELO. Se identificaron 37 artículos distribuidos en 13 países de Asia, Europa, América del Norte y Oceanía. Se observaron resultados perinatales adversos, tanto físicos como cognitivos, en la mayoría de los estudios. Los fármacos identificados como los más utilizados en los últimos años fueron valproato, topiramato, carbamazepina, lamotrigina y levetiracetam. Los FAE tienen potencial teratogénico en distintos grados de riesgo, provocando anomalías congénitas o efectos adversos en múltiples sistemas del cuerpo humano, siendo los sistemas nervioso, circulatorio y osteomuscular los más afectados.

The teratogenic risks caused by intrauterine exposure to antiepileptic drugs (AED) are known, so their prescription is kept under strict control. To describe the fetal adverse effects AED exposure during gestation, reported in the literature during the period 2016-2022. Systematized review of studies that reported fetal adverse effects induced for the exposure to AED in pregnant women in treatment for neurological diagnoses, mainly epilepsy. The search was carried out in PubMed, Cochrane, Web of Science, SCOPUS, Virtual Health Library, Lilacs and SciELO. 37 articles distributed in thirteen countries in Asia, Europe, North America and Oceania were identified. Adverse perinatal outcomes, both physical and cognitive, were observed in most studies. The most common drugs identified were valproate, topiramate, carbamazepine, lamotrigine and levetiracetam. AED have teratogenic potential in different degrees of risk, causing congenital anomalies or adverse effects in multiple systems of the human body, being the nervous, circulatory and musculoskeletal systems the most affected.

Tabaquismo durante el embarazo / Smoking during pregnancy

El tabaquismo durante el embarazo ha sido relacionado a muchas patologías obstétricas y neonatales, como desprendimiento de placenta, placenta previa, embarazo ectópico, aborto, parto prematuro, síndrome de distress respiratorio del recién nacido, bajo peso de nacimiento, muerte súbita, síndromes neurocognitivos, entre otros. En relación a la patología respiratoria el tabaquismo durante el embarazo produce alteraciones en la función de la vía aérea, traducido por flujos espiratorios disminuidos, sibilancias recurrentes y asma bronquial, hiperreactividad bronquial, mayor frecuencia de hospitalizaciones e infecciones respiratorias bajas. Finalmente es fundamental aplicar medidas tendientes a evitar el tabaquismo en las mujeres embarazadas y en el producto de la concepción.

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.

Reconstrução nasal neonatal na Síndrome do Warfarin Fetal / Neonatal nasal reconstruction in Fetal Warfarin Syndrome

O objetivo deste trabalho é relatar um caso de reconstrução nasal precoce em um paciente com síndrome do Warfarin fetal, onde um paciente de 23 dias com apresentava hipoplasia nasal isolada. O ganho ponderal estava estagnado e não havia possibilidade de introdução de sonda nasoentérica devido à deformidade. Foi realizada rinoplastia aberta com incisão transcolumelar. Dois enxertos de cartilagem tragal foram confeccionados e introduzidos na região da ponta, porção cranial do septo cartilaginoso e alares. O paciente apresentou melhoria da permeabilidade ventilatória, diminuição do ruído inspiratório, ganho de peso e também da forma. Após um ano de seguimento o resultado continuava satisfatório. Concluímos que a intervenção precoce é satisfatória e pode minimizar ou mesmo prevenir procedimentos futuros.

The aim of this work is to report a case of early nasal reconstruction in a 23-day-old patient with fetal Warfarin syndrome and isolated nasal hypoplasia. Weight gain was arrested and the deformity precluded the use of a nasogastric tube. An open rhinoplasty with transcolumellar incision was performed. Two grafts of tragal cartilage were made and introduced in the tip area, cranial portion of the cartilaginous septum, and alar cartilages. The patient presented improved ventilatory permeability, decrease of inspiratory noise, and weight and shape gains. At the one-year follow-up the result was still satisfactory. We concluded that early intervention is satisfactory and may minimize or even prevent future procedures.

Anticoagulation for pregnant patients with mechanical heart valves.

Management of a pregnant patient with mechanical heart valve is a complex issue for all health care providers involved in the care of such patients. Complications may arise at any stage due to the increased haemodynamic load imposed by pregnancy or because of impaired cardiac performance often seen in these patients. In addition, the use of various cardiovascular drugs in pregnancy (especially anticoagulants) may lead tofoetal loss or teratogenic complications. Additionally, the risk of thrombo-embolic complications in the mother is increased by the hypercoagulable state of pregnancy. In this review, we have attempted to draw inferences to guide management of such patients based on the available literature. It seems that in pregnant women with mechanical heart valves, recent data support warfarin use throughout pregnancy, followed by a switch to heparin and planned induction of labour. However, the complexity of this situation demands a cafeteria approach where the patient herself can choose from the available options that are supported by evidence-based information. Unfortunately there is no consensus on such data. An overview of the available literature forms the basis of this review. In conclusion, a guideline comprising pragmatic considerations is preffered.

Fetal warfarin syndrome.

Fetuses exposed to Warfarin in the first trimester of pregnancy have an increased risk of embryopathy which consists of nasal hypoplasia and stippled epiphyses, known as fetal warfarin syndrome or warfarin embryopathy. We herein report a first case of an infant with fetal warfarin syndrome in Thailand. The patient was an offspring of a 34-year-old mother with history of SLE and arterial embolism for several years. She had an unplanned pregnancy while taking warfarin. The patient developed difficulty breathing in the first few hours after birth from severe nasal hypoplasia. He also had short limbs, brachydactyly, nail hypoplasia, and calcifications in the epiphyseal regions of humeri, femora and vertebrae radiographically. The patient eventually died from respiratory failure at 6 months of age.

Adriamycin-induced fetal hydronephrosis

INTRODUCTION: At the end of pregnancy, the amniotic fluid (AF) depends basically on renal function, corresponding to fetal urine. Changes in AF, especially oligohydramnios, are reported in association with fetal hydronephrosis (FH). The experimental model using adriamycin in pregnant female rats has a teratogenic effect and has been classically employed to study esophageal atresia. Nevertheless, adriamycin promotes FH with high frequency as well. In the present study, using this animal model, we tried to identify the incidence and microscopic changes of FH, as well as its correlation with AF weight. MATERIALS AND METHODS: Eight Spreague-Dawley pregnant female rats received adriamycin 2.2 mg/kg on the 8th and 9th gestational days (considering term gestation = 22 days). Those fetuses that received adriamycin (Adriamycin Group) were compared with fetuses from 2 female rats (Control Group), which received 0.9 percent saline solution. On the 21.5 gestational day, the fetuses were collected by cesarean incision, sacrificed, and examined for macro and microscopic changes in kidneys and ureters. Fetuses with bilateral hydronephrosis formed the Hydronephrosis Group. AF weight was determined as well. RESULTS: Hydronephrosis occurred in 70 (95 percent) of the 74 fetuses in the adriamycin group against none of the 21 fetuses from the control group. The amniotic fluid weight was increased in the adriamycin group in relation to the control group (p < 0.001). The histomorphometric study revealed dilation of the renal pelvis and reduction of renal parenchyma in the hydronephrosis group in relation to the control group. Severe cortical atrophy, cortical tubular atrophy and medullar atrophy were observed in the hydronephrosis group. CONCLUSIONS: Slight renal lesions were in agreement with changes in AF weight, since they suggest that there was production of urine with the maintenance of AF.

Warfarin-associated Fetal Intracranial Hemorrhage: A Case Report

A 27-yr-old woman who had been taking warfarin for 10 yr after mitral valve replacement became pregnant. After knowing her pregnancy, she received heparinization for nine weeks instead of warfarin, and took oral anticoagulant again. At 24 weeks of gestation, fetal ultrasound and MRI showed a left subdural hematoma, and the pregnancy was terminated. Subdural hematoma was demonstrated on autopsy. Fatal bleeding of the fetus is a rare complication of maternal warfarin medication, occurring mostly in the second or third trimester. There is no alternative regimen available, so that regular monitoring by fetal ultrasound and strict control of warfarin dose with regular measurement of prothrombin time are the best way to prevent intrauterine fetal death due to bleeding.

Teratological effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): induction of cleft palate in the ddY and C57BL/6 mouse

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic halogenated aromatic hydrocarbon, is a teratogen to induce cleft palate when exposed during the pregnancy. There are inter-strain differences in the sensitivity to cleft palate induced by TCDD and other chemicals including polychlorinated terphenyls (PCTs). The C57BL/6 mouse and the ddY mouse had been shown to be different in the induction of cleft palate following the treatment of PCTs, which attempts us to evaluate the TCDD-induced cleft palate in two mouse strains to understand the mechanism through which TCDD and PCTs induce cleft palate. This study evaluated the induction of cleft palate in the fetuses of ddY and C57BL/6 mice after subcutaneous treatment of TCDD on gestation day (GD) 10.5-14.5 or oral treatment on GD 8.5-13.5. Our results clearly showed that ddY mice, a susceptible strain to PCTs-induced cleft palate, are resistant to the induction of cleft palate by TCDD comparably to the high susceptibility of C57BL/6 mice, suggesting a different teratological mechanism between TCDD and PCTs. In addition, at the low doses, our study supported the concept of "window effect" of TCDD on around GD 12 for the induction of cleft palate in C57BL/6 and ddY mice.

A case of prenatal diagnosis of fetal hydantoin syndrome by ultrasound

Fetal hydantoin syndrome (FHS) is a set of disruptions occasionally present in fetuses exposed in utero to phenytoin or other anticonvulsants. Administration of phenytoin in early pregnancy may impair proper psychomotor performance expected for children's development. Several combined phenotypic markers delineate the syndrome, but the presence of single clinical signs is more common. There is controversy about the etiology of FHS. Associated disruptions may be related to a deficiency in a detoxifying enzyme (epoxide hydrolase), vascular problems, and/or factors not yet known. Genetic causes are believed to influence susceptibility to the drug. This text reports an unusual pattern of malformations detected in an ultrasound scan (gastroschisis, sacral meningomyelocele, and absence of the right lower limb) and in the anatomopathological study (left-side gastroschisis, sacral meningomyelocele, scoliosis, left clubfoot, absence of the right lower limb, and pectus carinatum) of a fetus whose mother took phenytoin. These defects may have been provoked by exposure to the drug during embryogenesis. In view of similar malformations observed in cases of prenatal exposure to cocaine, a recognized vasoconstrictor, it is suggested that vascular disruptions of hemodynamic origin constituted the event leading to some of the anomalies caused in the developing embryo. A complication of the chorionic villus sampling procedure, used for cytogenetic analysis, is another possibility.

Consumo de fármacos en el embarazo / Drug consumption during pregnancy

El consumo de fármacos durante el embarazo es un fenómeno con implicaciones directas en el binestar materno-fetal que puede presentar variaciones entre comunidades, de donde surge la ncesidad de realizar estudios locales. Se realizaron 200 encuestas de acuerdo a una ficha precodificada a las mujeres que acudieron a la consulta externa del servicio de obstetricia del Hospital General "Dr. Manuel Gea González" para su control prenatal. La encuesta incluía los nombres de los productos, dosis, vía de administración, momento de embarazoen que fueron consumidos y la presencia de afecciones materna o enfermedades subyacentes. El promedio de productos consumidos fue dos con un rango de 0 a 6 únicamente se encontró relacionado con un incremento en la cantidad de afecciones maternas. Los fármacos más consumidos fuero los polivitamínicos (32 por ciento), antibióticos (24 por ciento), suplementación de hierro (9 por ciento), antieméticos (7 por ciento), antiinflamatorios no esteroideos (6 por ciento) y paracetamol (5 por ciento). El consumo de fármacos corresponde a una práctica de orden cultural independiente del nivel educativo o la edad de las mujeres. En algunos casos se prescribieron fármacos no clasificados o proscritos durante el embarazo. el patrón de consumo de medicamentos durante el embarazo se puede utilizar como un parámetro para evaluar la calidad de atención médica prenatal

Uso de cocaína na gravidez: análise dos riscos obstétricos e neonatais / Use of cocaine during pregnancy: an analysis of obstetrical risks and adverse effects on the fetus

O uso da cocaína durante a gravidez tem obtido destaque nas publicaçöes relacionadas a problemas de saúde na última década, Há uma estimativa de que 158.000 crianças por ano säo expostas a cocaína no útero nos Estados Unidos. Infelizmente no Brasil näo há estudos a esse respeito. Os riscos maternos do uso da cocaína durante a gravidez incluem descolamento prematuro de placenta, aborto espontâneo e rotura prematura das membranas. Os efeitos adversos no feto e no neonato incluem diminuiçäo do peso ao nascer e do tempo gestacional, retardo do crescimento fetal, anormalidades congênitas, síndrome da morte súbita na infância, acidente vascular cerebral, entre outros. Muitas dessas mudanças säo atribuidas a capacidade da cocaína em produzir alteraçöes vasculares tanto na mäe como no feto

Efeitos do etanol, benzodiazepínicos e antieméticos na gravidez / Effects of ethanol, benzodiazepines and antiemetic drugs in pregnancy

Os autores apresentam uma revisäo sobre o uso do etanol, benzodiazepínicos e antieméticos durante a gravidez e discutem os possiveis efeitos adversos sobre o feto