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.

Drug use during pregnancy and its consequences: A nested case control study on severe maternal morbidity / Uso de drogas na gestação e suas consequências: um estudo de caso-controle aninhado sobre morbidade materna grave

Abstract Objective To assess the relationship between the use of psychoactive substances during pregnancy and the occurrence of severe maternal morbidity (SMM), perinatal outcomes and repercussions on the neuropsychomotor development of exposed children. Methods A case-control study nested within a cohort of severe maternal morbidity (COMMAG) was performed. Women with SMM were considered cases. Controls were thosewith low-risk pregnancy,without SMMand admitted during the same time period as the cases. Cohort data were collected retrospectively in hospital records for childbirth. A face-to-face interview was also performed with 638 women (323 without SMM and 315 with SMM) and their children of the index pregnancy between 6 months and 5 years after childbirth. During the interview, substance abuse during pregnancy was assessed by a modified question from the Alcohol, Smoking and Substance Involvement Screening Test 2.0 (ASSIST) and the neuropsychomotor development in the children was assessed by the Denver Developmental Screening Test, 2nd edition. Results The prevalence of licit or illicit drug use during pregnancy was ~ 17%. Among drug users, 63.9% used alcohol, 58.3% used tobacco, 9.2% used cocaine/crack and 4.6% used marijuana. There was no association between drug use during pregnancy and SMM, although tobacco use during pregnancy was associated with bleeding, presence of near-miss clinical criteria (NMCC) and alteration in infant development; alcohol use was associated with neonatal asphyxia; and cocaine/crack use was associated with the occurrence of some clinical complications during pregnancy. Conclusion The use of psychoactive substances during pregnancy is frequent and associated with worse maternal, perinatal and child development outcomes.

Resumo Objetivo Avaliar a relação entre o uso de substâncias psicoativas na gestação e a ocorrência de morbidade materna grave (MMG), resultados perinatais e repercussões no desenvolvimento neuropsicomotor das crianças expostas. Métodos Estudo de caso-controle a partir de uma coorte de morbidade materna grave (COMMAG). Mulheres com MMG foram consideradas casos. Controles foram mulheres com gestação de baixo risco, admitidas no mesmo período que os casos. Os dados da coorte foram coletados retrospectivamente em prontuários de internação para o parto e entrevistas presenciais conduzidas com 638 mulheres e seus filhos da gestação-índice, entre 6 meses e 5 anos após o parto. Na entrevista, o uso de substâncias na gestação foi avaliado com uma pergunta modificada introduzida no questionário para triagem do uso de álcool, tabaco e outras substâncias 2.0 (ASSIST, na sigla em inglês) e o desenvolvimento neuropsicomotor das crianças foi avaliado pelo teste de triagem do desenvolvimento Denver II. Resultados A prevalência do uso de drogas lícitas ou ilícitas na gestação foi de cerca de 17%. Das usuárias, 63,9% usaram álcool, 58,3% usaram tabaco, 9,2% usaram cocaína/crack e 4,6% usaram maconha. Não houve associação entre o uso de drogas na gestação eMMG. Contudo, o uso de tabaco foi associado a hemorragia, presença de critérios clínicos de near miss e alteração no desenvolvimento infantil. O uso de álcool foi associado à asfixia neonatal e o uso de cocaína/crack à ocorrência de alguma complicação clínica na gestação. Conclusão O abuso de substâncias lícitas ou ilícitas na gestação é frequente e associado a piores desfechos maternos, perinatais e do desenvolvimento infantil.

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.

Contracepção e gravidez após transplante hepático: uma visão atual / Contraception and pregnancy after liver transplantation: an update overview

CONTEXTO: O transplante hepático bem sucedido não apenas cura a doença hepática de base, mas rapidamente restaura a libido e a fertilidade nas receptoras. Apesar do número crescente de gestações bem sucedidas em mulheres transplantadas, tais gestações são consideradas de alto risco, pois associam-se a maior morbidade materno-fetal. AQUISIÇÃO DE EVIDÊNCIA: Revisão de literatura indexada no MEDLINE (1978-2007) foi realizada empregando-se os termos "transplante hepático", "gravidez", imunossupressores", "função sexual". Artigos de revisão, estudos clínicos retrospectivos, estudos clínicos de seguimento de séries de pacientes e artigos originais, contendo observações de ciência básica relevante, foram incluídos. RESULTADOS: Embora não haja padronização dos cuidados na gravidez em receptoras de transplante hepático, existem algumas "regras de ouro" para aumentar a possibilidade de evolução materno-fetal favorável. A maioria dos centros recomenda adiar a gravidez pelo menos por 1 ano após o transplante hepático, quando habitualmente a paciente se encontra com imunossupressão estabilizada e função hepática adequada, sem evidência de disfunção renal ou hipertensão arterial não controlada. Devido à frequência aumentada de prematuridade, baixo peso ao nascer, hipertensão arterial e pré-eclâmpsia, a gestação após transplante hepático é considerada de alto risco e deve ser rigorosamente monitorada por equipe multidisciplinar, incluindo obstetra com experiência em gestações de alto risco. Controle frequente dos níveis séricos dos imunossupressores é prudente para evitar rejeição do enxerto e drogas com potencial teratogênico devem ser interrompidas. Aleitamento materno não é incentivado devido à excreção das drogas imunossupressoras no leite materno. CONCLUSÕES: Gestação bem sucedida é a regra após o transplante hepático desde que sejam observados certos cuidados. Controle médico rigoroso por equipe multidisciplinar experiente aumenta as chances de...

CONTEXT: Successful liver transplantation not only treats the underlying liver disease but also restores libido and fertility in female recipients. Although reports of successful pregnancy after liver transplantation continue to increase, these pregnancies are considered of high-risk because they are associated with increase maternofetal morbidity. EVIDENCE ACQUISITION: A MEDLINE search (1978-2007) was conducted using the terms "liver transplantation", "pregnancy", "immunosupressive agents", "sexual function". Reviews, retrospective series, long-term clinical follow-up of case series and original articles containing basic scientific observations were included. RESULTS: Although no formal guidelines have been established there are some "golden rules" to improve the probability of favorable maternal and fetal outcome. Most transplant centers recommend to delay pregnancy for at least 1-year after transplantation. The recipient should be on a stable immunosuppression regimen, with good graft function and no evidence of renal dysfunction or uncontrolled arterial hypertension. Considering the increased incidence of prematurity, low birth weight, hypertension and preeclampsia reported during pregnancy post-LT, these high-risk patients should be managed by a multidisciplinary team, including an obstetrician specialized in high-risk pregnancies. Carefully monitoring of immunosuppressive drugs serum level is prudent to avoid graft rejection episodes and drugs with teratogenic potential should be discontinued. Breastfeeding is usually not recommended. CONCLUSIONS: Successful pregnancies are the rule after liver transplantation. A carefully monitoring by an experience multidisciplinary team increases the chances of favorable maternofetal outcome.

Maternal and Neonatal Effects of Substance Abuse during Pregnancy: Our Ten-year Experience

PURPOSE: The aim of the study was to assess perinatal outcome of pregnancy burdened with maternal addiction in comparison with an unselected population from a European transition country. MATERIALS AND METHODS: Data on pregnancies complicated by illicit drug abuse (n = 85) managed during a 10-year period (1997-2007) at Split University Hospital were analyzed. Data on the type of drug, course of gestation and labor, and on perinatal outcome were considered. Data on all non-dependence pregnancies recorded during the study period were used as a control group. RESULTS: During the study period, there were 85 dependence-complicated pregnancies (0.2%). Use of heroin alone during pregnancy was recorded in 51 women (50%), methadone alone in 6 (7%), and a combination of heroin and methadone in 9 (11%). Premature delivery was significantly more common in the group of pregnant addicts (21% vs. 6%); 49% of pregnant addicts were carriers of hepatitis C virus (HCV) and 14% of hepatitis B virus (HBV). Neonatal abstinence syndrome developed in 61 infants (7%) born to addicted mothers. There were 4 cases (4.6%) of early neonatal death; 7 neonates had 5-minute Apgar score < or = 7 (8%); 29 neonates had low birth weight for age (33%); and 7 neonates had congenital anomalies (8%). The risk of various congenital anomalies was 3-fold in the group of children born to addicted mothers. CONCLUSION: Addiction pregnancies present a small but high-risk group according to perinatal outcome. Appropriate obstetric and neonatal care can reduce the rate of complications in these pregnancies and improve perinatal outcome.

Tratamiento farmacológico de enfermedades gastrointestinales durante el embarazo / Gastrointestinal medication in pregnancy

Medication of gastrointestinal disorders in the pregnancy, as well as of other pathological conditions, represent an important challenge for gastroenterologist and obstetrician. Several new medications has been developed in the last year and an adequate knowledge about the risks and benefits of different drugs involved in the treatment of these patients is very important. Classification of the drugs used in gastrointestinal diseases as well the available evidence of the effects these drugs during pregnancy is analyzed.

El tratamiento de las enfermedades gastrointestinales en el embarazo, así como otras condiciones patológicas, representa un importante desafió para los gastroenterólogos y obstetras. Nuevos medicamentos han sido desarrollados en el último tiempo y un adecuado conocimiento sobre los riesgos y beneficios de las diferentes drogas involucradas en el tratamiento de estas pacientes es muy importante. La clasificación de las drogas usadas en las enfermedades gastrointestinales, así como la evidencia disponible de los efectos de estos medicamentos durante el embarazo es analizada.

Arsenic exposure in pregnancy: a population-based study in Matlab, Bangladesh.

This study assessed the exposure of pregnant women to arsenic in Matlab, Bangladesh, an area with highly-elevated concentrations of arsenic in tubewells, by measuring concentrations of arsenic in urine. In a defined administrative area, all new pregnancies were identified by urine test in gestational week 6-8, and women were asked to participate in the assessment of arsenic exposure. Urine for analysis of arsenic was collected immediately and in gestational week 30. In total, 3,426 pregnant women provided urine samples during January 2002-March 2003. There was a considerable variation in urinary concentrations of arsenic (total range 1-1,470 microg/L, adjusted to specific gravity 1.012 g/mL), with an overall median concentration of 80 microg/L (25th and 75th percentiles were 37 and 208 microg/L respectively). Similar concentrations were found in gestational week 30, indicating no trend of decreasing exposure, despite the initiation of mitigation activities in the area. Arsenic exposure was negatively associated with socioeconomic classes and achieved educational level. There were marked geographical variations in exposure. The results emphasize the urgent need for efficient mitigation activities and investigations of arsenic-related reproductive effects.

Infección por virus de inmunodeficiencia humana en el embarazo: tratamiento anti-retroviral y vía de parto / Human immunodeficiency virus (HIV) infection in pregnancy: antiretroviral treatment (ART) and mode of delivery

La terapia anti-retroviral utilizada durante el embarazo en madres infectadas con VIH disminuye la transmisión perinatal del virus. Esto es válido para mono, bi y tri-terapia (HAART), siendo mayor el efecto de esta última. Sin embargo, cuando se utilizan dichas terapias se debe tener en consideración riesgos potenciales para la madre e hijo (hiperglicemia, acidosis láctica, toxicidad mitocondrial, rash cutáneo, daño hepático, síndrome hipertensivo y parto prematuro). La operación cesárea electiva reduce la transmisión perinatal del virus en pacientes sin terapia o monoterapia. Con tri-terapia este beneficio no está demostrado. Este artículo revisa la evidencia de efectos benéficos y adversos de la terapia anti-retroviral y de la operación cesárea y propone una pauta de manejo de las pacientes infectadas con VIH en el embarazo.

Perinatal effects of amphetamine and heroin use during pregnancy on the mother and infant.

OBJECTIVES: To determine the perinatal impacts of heroin and amphetamine on both mothers and infants. MATERIAL AND METHOD: This is a retrospective study on the influence of amphetamine and heroin on pregnant women and their newborn infants at King Chulalongkorn Memorial Hospital in Bangkok, Thailand, between January 1997 and December 2002. The medical and demographic data of both mothers and infants were evaluated. Comparison of the consistent drug effects of these 2 drugs on the mothers and infants were also performed RESULTS: Two hundred and eleven women were identified There were 178 (84.4%) and 33 (15.6%) women addicted to amphetamine and heroin respectively. Sixty one (28.9%) of them were polydrug users. There were more polydrug users among heroin addicts than amphetamine addicts, (43.7% vs 27.2%, p < 0.05). Poor obstetric history were noted in both groups of women including lack of prenatal care (74.9%), a high incidence of previous abortion (22.3%), positive HIV serology test (11.1%), pre-eclampsia (5.2%), infection (3.3%) and antepartum hemorrhage (1.9%). Drug intoxication was found in 11 amphetamine addicted mothers, whereas 2 heroin addicts developed withdrawal symptoms during intrapartum and postpartum periods. All infants were singleton. There was one stillbirth and 2 neonatal deaths. There was no statistical difference in terms of sex ratio, mean birth weight, gestational age, length, head circumference and Apgar score between the groups of amphetamine and heroin exposed infants. The incidence of prematurity, low birth weight, IUGR and microcephaly were not statistically different between both groups of infants. The overall incidence was 31.7%, 31.7%, 9.5% and 8.6% respectively. Congenital anomalies were found in 5 (2.8%) amphetamine exposed infants. Thirty one out of 33 heroin exposed infants (93.9%) and 4 out of 178 amphetamine exposed infants (2.2%) developed drug withdrawal symptoms with the mean onset of 21.5 +/- 16.5 hours and 10.3 +/- 7.5 hours respectively, p > 0.05. All heroin withdrawal infants were successfully treated with Phenobarbital with the mean duration of treatment of 23.7 +/- 11.5 days. None of the amphetamine withdrawal infants needed specific treatment. They recovered spontaneously within 6.0 +/- 5.3 days. Eighteen infants were left in an orphanage or under the custody of their relatives. CONCLUSION: Amphetamine or heroin use during pregnancy can cause many serious adverse effects on both mothers and infants. The findings in the present study are consistent with previous reports, although they seemed to be more common and severe. Increasing awareness and improving understanding of drug abuse in the medical, legal and social aspects are needed in order to reduce these impacts.

Terapia con metformina y embarazo en pacientes con síndrome de ovario poliquístico / Metformin therapy for polycystic ovary syndrome during pregnancy

Estudio prospectivo de seguimiento de 15 pacientes con síndrome de ovario poliquístico (SOP) e hiperinsulinemia que se embarazaron con el uso de metformina, y que se siguieron hasta el parto. Diez continuaron metformina durante el embarazo, hasta las 14 semanas y cinco hasta las 32 semanas. Las 5 pacientes que usaron más tiempo el medicamento no desarrollaron diabetes gestacional a diferencia de las que lo tomaron hasta las 14 semanas que presentaron diabetes gestacional en tres de diez. No encontramos abortos en estas pacientes, y tampoco presentaron problemas con el medicamento. No hubo malformaciones en los recién nacidos.

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

Epilepsia, neuroendocrinologia e obstetrícia / Epilepsy, neuroendocrinoly and obstetrins

Esta revisão levanta questões sobre hormônios, epilepsia e gravidez. A relação entre crises generalizadas ou parciais e hormônios é considerada, e também, o vínculo entre hormônios sexuais e crises como as catameniais. A redução da libido pode estar relacionada às drogas antiepiléticas (DAE) e distúrbios hormonais. As DAE podem induzir malformações congênitas e redução da eficácia de contraceptivos orais. A orientação sobre o cuidado da mulher epilética em idade procriativa pela Liga International contra a Epilepsia é apresentada.

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