RESUMEN
The objective of the study was to evaluate the rate of major congenital anomalies after first trimester exposure to ondansetron for nausea and vomiting of pregnancy (NVP). The design is a prospective, comparative, observational cohort study, performed at the Israeli Teratology Information Service between 2010 and 2014. Follow-up was obtained for 195 ondansetron-exposed, 110 metoclopramide-exposed, and 778 pregnancies with non-teratogenic exposure (NTE). The overall rate of major anomalies did not significantly differ between the groups [4/200 = 2.0 % (ondansetron), 1/109 = 0.9 % (metoclopramide), and 13/731 = 1.8 % (NTE)]. All the anomalies in both the ondansetron and metoclopramide groups, and 6/13 anomalies in the NTE group, were cardiac septal defects most of which spontaneously resolved. Both ondansetron (adjHR = 0.29, 95 % CI 0.10-0.80) and metoclopramide (adjHR = 0.27, 95 % CI 0.08-0.86) were associated with lower miscarriage rate compared to NTE. Based on the present study, ondansetron during pregnancy is not associated with an increased risk for overall major anomalies, nor for clinically important cardiac defects. It may be a reasonable alternative for women with severe NVP who do not respond to first line medications.
Asunto(s)
Anomalías Inducidas por Medicamentos/epidemiología , Antieméticos/toxicidad , Metoclopramida/toxicidad , Ondansetrón/toxicidad , Adolescente , Adulto , Niño , Preescolar , Femenino , Defectos de los Tabiques Cardíacos/epidemiología , Humanos , Masculino , Intercambio Materno-Fetal , Náusea/tratamiento farmacológico , Embarazo , Resultado del Embarazo , Estudios Prospectivos , Vómitos/tratamiento farmacológico , Adulto JovenRESUMEN
INTRODUCTION: Methylphenidate is a central nervous system stimulant medicinally used in the treatment of attention-deficit disorder with or without hyperactivity (ADD/ADHD). Data on its use in human pregnancy are limited. The primary objective of the study was to evaluate the risk of major congenital anomalies after pregnancy exposure to methylphenidate for medical indications. METHODS: In a prospective, comparative, multicenter observational study performed in 4 participating Teratology Information Services (in Jerusalem, Berlin, Newcastle upon Tyne, and Toronto) between 1996 and 2013, methylphenidate-exposed pregnancies were compared with pregnancies counseled for nonteratogenic exposure (NTE) after matching by maternal age, gestational age, and year at initial contact. RESULTS: 382 methylphenidate-exposed pregnancies (89.5% in the first trimester) were followed up. The overall rate of major congenital anomalies was similar between the groups (10/309 = 3.2% [methylphenidate] vs 13/358 = 3.6% [NTE], P = .780). The rates of major congenital anomalies (6/247 = 2.4% [methylphenidate] vs 12/358 = 3.4% [NTE], P = .511) and cardiovascular anomalies (2/247 = 0.8% [methylphenidate] vs 3/358 = 0.8% [NTE], P = .970) were also similar after exclusion of genetic or cytogenetic anomalies and limiting methylphenidate exposure to the period of organogenesis (weeks 4-13 after the last menstrual period). There was a higher rate of miscarriages and elective terminations of pregnancy in the methylphenidate group. Significant predictors for the miscarriages using Cox proportional hazards model were methylphenidate exposure (adjusted hazard ratio [HR] = 1.98; 95% CI, 1.23-3.20; P = .005) and past miscarriage (adjusted HR = 1.35; 95% CI, 1.18-1.55; P < .001). CONCLUSIONS: The present study suggests that methylphenidate does not seem to increase the risk for major malformations. Further studies are required to establish its pregnancy safety and its possible association with miscarriages.
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Anomalías Inducidas por Medicamentos/etiología , Aborto Inducido/estadística & datos numéricos , Aborto Espontáneo/epidemiología , Anomalías Cardiovasculares/epidemiología , Estimulantes del Sistema Nervioso Central/efectos adversos , Metilfenidato/efectos adversos , Complicaciones del Embarazo/tratamiento farmacológico , Anomalías Inducidas por Medicamentos/epidemiología , Anomalías Cardiovasculares/inducido químicamente , Femenino , Estudios de Seguimiento , Humanos , Embarazo , Complicaciones del Embarazo/epidemiología , RiesgoRESUMEN
This multicenter, observational prospective cohort study addresses the risk associated with exposure to mirtazapine during pregnancy. Pregnancy outcomes after exposure to mirtazapine were compared with 2 matched control groups: (1) exposure to any selective serotonin reuptake inhibitor (SSRI, control subjects with a psychiatric condition) and (2) no exposure to medication known to be teratogenic or any antidepressant (general control subjects). Data were collected by members of the European Network of Teratology Information Services between 1995 and 2011. Observations from 357 exposed pregnancies were compared with 357 pregnancies from each control group. The rate of major birth defects between the mirtazapine and the SSRI group did not differ significantly (4.5% vs 4.2%; odds ratio [OR], 1.1; 95% confidence interval [95% CI], 0.5-2.3; P = 0.9). A trend toward a higher rate of birth defects in the mirtazapine group compared with general control subjects (4.5% vs 1.9%; OR, 2.4; 95% CI, 0.9-6.3; P = 0.08) reached statistical significance after exclusion of chromosomal or genetic anomalies (4.1% vs 1.3%; OR, 3.3; 95% CI, 1.04-10.3; P = 0.03), but this difference became again nonsignificant if cases of exposure not comprising the first trimester were excluded from the analysis (3.4% vs 1.9%; OR, 1.8; 95% CI, 0.6-5.0; P = 0.26). The crude miscarriage rate did not differ significantly between the mirtazapine, the SSRI, and the general control groups (12.1% vs 12.0% vs 9.3%; P = 0.44). However, a higher rate of elective pregnancy termination was observed in the mirtazapine group compared with SSRI and general control subjects (7.8% vs 3.4% vs 5.6%; P = 0.03). This study did not observe a statistically significant difference in the rate of major birth defects after first-trimester exposure between mirtazapine, SSRI-exposed, and nonexposed pregnancies. A marginally higher rate of birth defects was, however, observed in the mirtazapine and SSRI groups compared with the low rate of birth defects in our general control subjects. Overall pregnancy outcome after mirtazapine exposure was similar to that of the SSRI-exposed control group.
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Antidepresivos/efectos adversos , Mianserina/análogos & derivados , Resultado del Embarazo/epidemiología , Anomalías Inducidas por Medicamentos/epidemiología , Anomalías Inducidas por Medicamentos/etiología , Adulto , Peso al Nacer/efectos de los fármacos , Estudios de Casos y Controles , Trastorno Depresivo/complicaciones , Trastorno Depresivo/tratamiento farmacológico , Femenino , Edad Gestacional , Humanos , Mianserina/efectos adversos , Mirtazapina , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/psicología , Estudios Prospectivos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversosRESUMEN
OBJECTIVE: The authors conducted a prospective, comparative observational study to evaluate the risk of major anomalies following exposure to lithium during pregnancy. METHOD: A total of 183 lithium-exposed pregnancies of women who contacted the Israeli Teratology Information Service were followed up (90.2% in the first trimester) and compared with 72 disease-matched and 748 nonteratogenic-exposed pregnancies. RESULTS: There were significantly more miscarriages (adjusted odds ratio=1.94, 95% CI=1.08-3.48) and elective terminations of pregnancy (17/183 [9.3%] compared with 15/748 [2.0%]) in the lithium-exposed group compared with the nonteratogenic exposure group. The rate of major congenital anomalies after exclusion of genetic or cytogenetic anomalies was not significantly different between the three groups (lithium-exposed in the first trimester: 8/123 [6.5%]; bipolar: 2/61 [3.3%]; nonteratogenic: 19/711 [2.7%]). Cardiovascular anomalies occurred more frequently in the lithium group exposed during the first trimester when compared with the nonteratogenic exposure group (5/123 [4.1%] compared with 4/711 [0.6%]) but not after excluding anomalies that spontaneously resolved (3/123 [2.4%] compared with 2/711 [0.3%]). Ebstein's anomaly was diagnosed in one lithium-exposed fetus and in two retrospective lithium cases that were not included because contact with the information service was made after the prenatal diagnosis by ultrasound. The rate of noncardiovascular anomalies was not significantly different between the groups. The rate of preterm deliveries was higher in the lithium group compared with the nonteratogenic exposure group (18/131 [13.7%] compared with 41/683 [6.0%]). CONCLUSIONS: Lithium treatment in pregnancy is associated with a higher rate of cardiovascular anomalies. Women who are treated with lithium during organogenesis should undergo fetal echocardiography and level-2 ultrasound.
Asunto(s)
Anomalías Inducidas por Medicamentos/etiología , Aborto Espontáneo/inducido químicamente , Trastorno Bipolar/tratamiento farmacológico , Compuestos de Litio/toxicidad , Resultado del Embarazo , Efectos Tardíos de la Exposición Prenatal , Anomalías Inducidas por Medicamentos/diagnóstico , Aborto Eugénico/estadística & datos numéricos , Aborto Espontáneo/diagnóstico , Adulto , Femenino , Humanos , Recién Nacido , Compuestos de Litio/uso terapéutico , Masculino , Trabajo de Parto Prematuro/inducido químicamente , Embarazo , Primer Trimestre del Embarazo , Factores de Riesgo , Ultrasonografía PrenatalRESUMEN
OBJECTIVE: To examine first trimester safety of angiotensin-converting-enzyme-inhibitors (ACEIs) or angiotensin-receptor-blockers (ARBs). STUDY DESIGN: Prospective observational cohort regarding pregnancy ACEI/ARBs-exposure including contacts to two Teratology Information Services in Israel (1994-2007) and Italy (1990-2008), with two comparison groups: (1) exposed to other antihypertensives (OAH) (2) after non-teratogenic exposure (NTE) in similar time frames. RESULTS: 252 ACEI/ARBs-exposed, 256 OAH-exposed and 495 NTE-exposed pregnancies were followed-up. The rate of major congenital anomalies was comparable between the groups (8/190, 4.2%, ACEI/ARB; 9/212, 4.2%, OAH; 18/471, 3.8% NTE; p = 0.954) among first trimester exposed pregnancies. The median gestational age at delivery was two weeks earlier, rate of preterm deliveries more than 2-fold higher, and median birth weight more than 200 g lower in the ACEI/ARB and OAH groups compared to the NTE group. CONCLUSION: The present study suggests that ACEI/ARBs are not major teratogens when used in the first trimester, and can reassure women with similar exposures.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Exposición Materna , Complicaciones del Embarazo/inducido químicamente , Anomalías Inducidas por Medicamentos/etiología , Adulto , Análisis de Varianza , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/administración & dosificación , Peso al Nacer/efectos de los fármacos , Distribución de Chi-Cuadrado , Femenino , Edad Gestacional , Humanos , Recién Nacido , Israel/epidemiología , Italia/epidemiología , Intercambio Materno-Fetal , Embarazo , Complicaciones del Embarazo/epidemiología , Primer Trimestre del Embarazo , Nacimiento Prematuro/inducido químicamente , Estudios Prospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
OBJECTIVE: We sought to examine the fetal safety of colchicine. STUDY DESIGN: This was a prospective observational comparative cohort study regarding colchicine exposure during pregnancy including contacts to 2 Teratology Information Services in Israel from 1994 through 2006. RESULTS: In all, 238 colchicine-exposed pregnancies (97.0% first trimester) and 964 pregnancies with nonteratogenic exposure were followed up. Treatment indications were: familial Mediterranean fever (87.3%), Behçet disease (7.5%), or other (5.2%). The rate of major congenital anomalies was comparable between the groups (10/221 [4.5%] vs 35/908 [3.9%]; P = .648). There were no cytogenetic anomalies in the colchicine group. The median gestational age at delivery was earlier (39 [38-40] vs 40 [38-41] weeks; P < .001), the rate of preterm deliveries was higher (32/214 [15.0%] vs 51/867 [5.9%]; P < .001), and the median birthweight was lower (3000 [2688-3300] vs 3300 [2900-3600] g; P < .001) in the colchicine group. CONCLUSION: The present study suggests that colchicine does not appear to be a major human teratogen, and, probably, has no cytogenetic effect.
Asunto(s)
Anomalías Inducidas por Medicamentos/diagnóstico , Anomalías Inducidas por Medicamentos/epidemiología , Colchicina/efectos adversos , Feto/efectos de los fármacos , Exposición Materna/efectos adversos , Resultado del Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Adulto , Síndrome de Behçet/tratamiento farmacológico , Peso al Nacer , Estudios de Cohortes , Colchicina/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Fiebre Mediterránea Familiar/diagnóstico , Fiebre Mediterránea Familiar/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Israel , Intercambio Materno-Fetal/efectos de los fármacos , Trabajo de Parto Prematuro , Embarazo , Primer Trimestre del Embarazo , Probabilidad , Estudios Prospectivos , Medición de Riesgo , Estadísticas no Paramétricas , TeratógenosRESUMEN
OBJECTIVE: To assess the safety of calcium channel blockers during the first trimester of pregnancy. STUDY DESIGN: A multicenter (n=11), prospective observational study of the European Network of Teratology Information Services (ENTIS). The rate of major birth defects was compared between a cohort of pregnant women exposed to calcium channel blockers during the first trimester (n=299) and a control group not exposed to potential teratogens (n=806). RESULTS: Major birth defects were not more common in the study group than in the control group. Birth weight was significantly lower in exposed term newborns. There were more preterm infants in the study group than in the control group (23.8% vs. 6.5%). These adverse effects are more likely due to the underlying disease than to the medication. CONCLUSION: This study suggests that calcium channel blockers during the first trimester of pregnancy do not represent a major teratogenic risk.
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Anomalías Inducidas por Medicamentos/etiología , Aborto Espontáneo/etiología , Bloqueadores de los Canales de Calcio/efectos adversos , Nacimiento Prematuro/etiología , Anomalías Inducidas por Medicamentos/epidemiología , Aborto Espontáneo/epidemiología , Adolescente , Adulto , Peso al Nacer , Europa (Continente)/epidemiología , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Israel/epidemiología , Persona de Mediana Edad , Embarazo , Primer Trimestre del Embarazo , Nacimiento Prematuro/epidemiología , Estudios ProspectivosRESUMEN
BACKGROUND: Epstein-Barr virus (EBV) is one of the most common human viruses. To date, there is limited information regarding the influence of maternal EBV infection on pregnancy outcome. OBJECTIVE: Our aim was to examine the fetal safety of EBV infection in pregnancy. STUDY DESIGN: We prospectively evaluated the rate of major anomalies and pregnancy outcome of women with serologic evidence of primary, recurrent or undefined infection (27, 56, and 43 women, respectively) compared to 1434 women who called the Israeli TIS for non-teratogenic exposure. RESULTS: Women's characteristics and pregnancy outcome were comparable between the EBV exposed and control groups. Similarly, the gestational age at delivery and birth weight were not significantly different. The rate of major congenital anomalies did not significantly differ between the EBV exposed compared to the control group. CONCLUSION: This study suggests that EBV infection during pregnancy does not represent a major teratogenic risk to the fetus.
Asunto(s)
Infecciones por Virus de Epstein-Barr/epidemiología , Resultado del Embarazo/epidemiología , Adulto , Femenino , Humanos , Israel/epidemiología , Embarazo , Estudios ProspectivosRESUMEN
In spite of a substantial increase in the use of topiramate at child bearing age, very little is known regarding its use in pregnancy. We describe the outcome of 52 pregnancies with 41 liveborn infants from which it seems that topiramate reduces birth weight without decreasing gestational age at delivery, but does not seem to increase the risk for structural defects. There was an increased rate of spontaneous abortions not related to the drug effects.
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Anomalías Inducidas por Medicamentos , Aborto Espontáneo/inducido químicamente , Anticonvulsivantes/toxicidad , Peso al Nacer/efectos de los fármacos , Fructosa/análogos & derivados , Femenino , Fructosa/toxicidad , Humanos , Recién Nacido , Embarazo , TopiramatoRESUMEN
BACKGROUND: Valproate is a first-line antiepileptic agent and is also used in the treatment of bipolar disorder and migraine. It is a known human teratogen. The objective of the study was to evaluate the teratogenic risk of valproate. METHODS: All callers who contacted the Israeli Teratology Information Service (TIS) between 1994 and 2004 for information about gestational exposure to valproate were enrolled in the study. After the expected date of delivery, these women were followed up by telephone interview about their pregnancy outcome using a structured questionnaire. Data obtained from women who contacted the TIS about valproate exposure during pregnancy were then compared with data obtained from callers who were counselled for nonteratogenic exposures over the same timeframe. The main outcome measure was the rate of major congenital anomalies. RESULTS: The outcomes of 154 valproate-exposed pregnancies (96.1% at least in the first trimester) were compared with those of 1315 pregnancies of women in the TIS database who were counselled for nonteratogenic exposures. The rate of major anomalies (some multiple) in the valproate group exposed in the first trimester was higher compared with controls after exclusion of genetic or cytogenetic anomalies (8 of 120 [6.7%] vs 31 of 1236 [2.5%], p = 0.018, relative risk [RR] = 2.66, 95% CI 1.25, 5.65). There were no cases of neural tube defect in the valproate-exposed group. Five of the eight major anomalies in the valproate group were cardiovascular, two of eight were mentally retarded, two of five male infants with major anomalies had hypospadias and three of eight were suspected of having fetal valproate syndrome. A daily dose > or =1000 mg was associated with the highest teratogenic risk (7 of 32 [21.9%] vs 31 of 1236 [2.5%], RR = 8.72, 95% CI 4.16, 18.30). In the subgroup exposed to polytherapy there was a 4-fold increase in the rate of major anomalies compared with controls. All major anomalies were in the group treated for epilepsy. CONCLUSION: When valproate treatment cannot be avoided in the first trimester of pregnancy, the lowest effective dose should be prescribed, preferably as monotherapy, to minimize its teratogenic risk.
Asunto(s)
Anomalías Inducidas por Medicamentos/etiología , Antimaníacos/efectos adversos , Resultado del Embarazo , Efectos Tardíos de la Exposición Prenatal , Ácido Valproico/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Embarazo , TeratologíaRESUMEN
Vitamin K antagonists (VKA) are known to act as teratogens; however, there is still uncertainty about the relative risk for birth defects and the most sensitive period. In a multi-centre (n = 12), observational, prospective study we compared 666 pregnant women exposed to phenprocoumon (n = 280), acenocoumarol (n = 226), fluindione (n = 99), warfarin (n = 63) and phenindione (n = 2) to a non-exposed control group (n = 1,094). Data were collected by institutes collaborating in the European Network of Teratology Information Services (ENTIS) during individual risk counselling between 1988 and 2004. Main outcome measures were coumarin embryopathy and other birth defects, miscarriage rate, birth-weight, and prematurity. The rate of major birth defects after 1st trimester exposure was significantly increased (OR 3.86, 95% CI 1.86-8.00). However, there were only two coumarin embryopathies (0.6%; both phenprocoumon). Prematurity was more frequent (16.0% vs. 7.6%, OR 2.61, 95% CI 1.76-3.86), mean gestational age at delivery (37.9 vs.39.4, p<0.001), and mean birth weight of term infants (3,166 g vs. 3,411 g; p < 0.001) were lower compared to the controls. Using the methodology of survival analysis, miscarriage rate reached 42% vs. 14% (hazard ratio 3.36; 95% CI 2.28-4.93). In conclusion, use of VKA during pregnancy increases the risk of structural defects and other adverse pregnancy outcomes. The risk for coumarin embryopathy is, however, very small, in particular when therapy during the 1(st) trimester did not take place later than week 8 after the 1(st) day of the last menstrual period. Therefore, elective termination of a wanted pregnancy is not recommended if (inadvertent) exposure took place in early pregnancy. Close follow-up by the obstetrician including level II ultrasound should be recommended in any case of VKA exposure during pregnancy.
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Anomalías Inducidas por Medicamentos , Aborto Espontáneo/etiología , Anticoagulantes/efectos adversos , Peso al Nacer/efectos de los fármacos , Enfermedades Fetales/etiología , Resultado del Embarazo , Vitamina K/antagonistas & inhibidores , Aborto Inducido , Acenocumarol/efectos adversos , Sistemas de Registro de Reacción Adversa a Medicamentos , Femenino , Edad Gestacional , Humanos , Fenindiona/efectos adversos , Fenindiona/análogos & derivados , Fenprocumón/efectos adversos , Embarazo , Primer Trimestre del Embarazo , Nacimiento Prematuro/etiología , Estudios Prospectivos , Warfarina/efectos adversosRESUMEN
AIM: To assess the teratogenic effect of metamizol when used during the first trimester of pregnancy. METHODS: One hundred and eight women who used metamizol during the first trimester of pregnancy were recruited from 4 teratogen information centers in Israel (3) and in Italy (1). The study group was paired for age, smoking habits and alcohol consumption with a comparative group exposed to acetaminophen. RESULTS: Maternal demographics and history, birth weight, gestational age at delivery, rate of live births, spontaneous abortions and fetal distress were comparable in both groups. The rate of major malformations in the metamizol group (3%) did not differ significantly from the rate in the comparative group (2%) (P = 0.57, relative risk = 1.55, 95% confidence interval 0.26-9.05). CONCLUSIONS: Our data may suggest that exposure to metamizol during the first trimester of pregnancy is probably not associated with a significantly increased risk for malformations or spontaneous abortions.
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Antiinflamatorios no Esteroideos/efectos adversos , Anomalías Congénitas/epidemiología , Dipirona/efectos adversos , Aborto Espontáneo/epidemiología , Adulto , Femenino , Humanos , Embarazo , Resultado del Embarazo , Primer Trimestre del Embarazo , Factores de RiesgoRESUMEN
OBJECTIVE: To assess the safety of the butyrophenone neuroleptics haloperidol and penfluridol in pregnancy. METHOD: The rate of major anomalies was compared between a cohort of pregnant women counseled for gestational exposure to haloperidol or penfluridol and a control group counseled for nonteratogen exposure. This multicenter, prospective, controlled study was conducted within the European Network of Teratology Information Services (ENTIS) and included women who contacted 1 of 4 teratology information services for counseling between January 1989 and December 2001. RESULTS: We followed up on the outcomes of 215 pregnancies exposed to haloperidol (N = 188) or penfluridol (N = 27)-78.2% (of 206) were in the first trimester-and compared to outcomes of 631 ENTIS controls. The rate of congenital anomalies did not differ between the haloperidol/penfluridol-exposed group and the control group (6/179 = 3.4% vs. 22/581 = 3.8%, p = .787). No difference was found by limiting the analysis to those exposed to butyrophenones during the first trimester. There were 2 cases of limb defects in the butyrophenone-exposed group (1 after haloperidol and 1 after penfluridol exposure) and none in the controls. A higher rate of elective terminations of pregnancy (8.8% vs. 3.8%, p = .004), a higher rate of preterm birth (13.9% vs. 6.9%, p = .006), a lower median birth weight (3155 g vs. 3370 g, p < .001), and a lower median birth weight of full-term infants (3250 g vs. 3415 g, p = .004) were found in the butyrophenone-exposed group compared to the controls. CONCLUSION: This study suggests that haloperidol and penfluridol do not represent a major teratogenic risk. Since a possible association between butyrophenone exposure and limb defects cannot be ruled out with this sample size, a level II ultrasound with emphasis on the limbs should be considered in pregnancies with first trimester exposure.
Asunto(s)
Anomalías Inducidas por Medicamentos/epidemiología , Antipsicóticos/efectos adversos , Haloperidol/efectos adversos , Exposición Materna/estadística & datos numéricos , Penfluridol/efectos adversos , Complicaciones del Embarazo/tratamiento farmacológico , Anomalías Inducidas por Medicamentos/diagnóstico , Anomalías Inducidas por Medicamentos/etiología , Adulto , Antipsicóticos/uso terapéutico , Peso al Nacer , Butirofenonas/efectos adversos , Butirofenonas/uso terapéutico , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Edad Gestacional , Haloperidol/uso terapéutico , Humanos , Recién Nacido , Intercambio Materno-Fetal , Paridad , Penfluridol/uso terapéutico , Embarazo , Resultado del Embarazo/epidemiología , Primer Trimestre del Embarazo , Nacimiento Prematuro/inducido químicamente , Nacimiento Prematuro/epidemiología , Estudios ProspectivosRESUMEN
AIMS: The number of published studies on the use of amoxycillin/clavulanic acid during pregnancy is small and so is the number of pregnancies investigated in those studies. In this study we wished to investigate prospectively the safety of intrauterine exposure to amoxycillin/clavulanic acid in a relatively large cohort of women. METHODS: Women treated (n = 191) with amoxycillin/clavulanic acid during the first trimester of pregnancy were recruited from two teratogen information centres in Israel. Exposed women were matched for age, smoking habits and alcohol consumption with 191 controls exposed to amoxycillin only for similar medical indications. RESULTS: Maternal age, birth weight, gestational age at delivery, rates of live births and abortions were comparable between the two groups. Rates of major malformations in the amoxycillin/clavulanic acid group (3/158, 1.9%) did not differ significantly from controls (5/163, 3%) (P = 0.49, relative risk = 0.62, 95% confidence interval 0.15, 2.55), and were within the expected baseline risk for the general population. CONCLUSION: These data suggest that exposure to amoxycillin/clavulanic acid during pregnancy is unlikely to be associated with an increased risk of malformations.
Asunto(s)
Amoxicilina/efectos adversos , Antibacterianos/efectos adversos , Ácido Clavulánico/efectos adversos , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo , Primer Trimestre del Embarazo , Estudios ProspectivosRESUMEN
OBJECTIVE: To evaluate the safety of glucocorticosteroids (GCS) in pregnancy. STUDY DESIGN: The Israeli Teratogen Information Service (TIS) prospectively collected and followed 311 pregnancies counseled regarding systemic use of different GCS in the first trimester. The rate of major congenital anomalies was compared to that of 790 controls who were counseled for non-teratogenic exposure. RESULTS: The rate of major anomalies did not significantly differ between the groups [12/262 = 4.6% (GCS), 19/728 = 2.6% (control), [P = 0.116 ]. There was no case of oral cleft and no pattern of anomalies among the GCS exposed group. Higher rates of miscarriages (11.5% versus 7.0%, P = 0.013) and preterm births (22.7% versus 10.8%, P < 0.001 ) were observed among the GCS exposed group compared to the controls. GCS exposed infants had a lower median birth weight [3080 g versus 3290 g, P < 0.001 ] and were born at an earlier median gestational age [39 weeks versus 40, P < 0.001 ] compared to the control. CONCLUSIONS: The present study supports that GCS do not represent a major teratogenic risk in humans. The study was powered to find a 2.5-fold increase in the overall rate of major anomalies.
Asunto(s)
Anomalías Inducidas por Medicamentos , Aborto Espontáneo/inducido químicamente , Peso al Nacer/efectos de los fármacos , Glucocorticoides/toxicidad , Trabajo de Parto Prematuro/inducido químicamente , Adulto , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Embarazo , Primer Trimestre del Embarazo , Estudios ProspectivosRESUMEN
BACKGROUND: Loratadine is a second-generation histamine H(1)-receptor antagonist, used in the treatment of allergic conditions. No prospective controlled trials on loratadine in human pregnancy have been published to date. OBJECTIVE: To determine whether the use of loratadine or other antihistamines (OAH) is associated with an increased risk of major anomalies. METHODS: Callers who were counseled by the Israeli Teratogen Information Service in regard to loratadine or OAH exposure during pregnancy were prospectively collected and followed up. Pregnancy outcome was compared among three exposure groups: loratadine, OAH, and a control group of patients who were counseled for nonteratogenic exposure, nonteratogenic controls (NTC). The OAH included astemizole, chlorpheniramine, terfenadine, hydroxyzine, promethazine, and dimetindene. RESULTS: We followed up 210 pregnancies exposed to loratadine (77.9% in the first trimester) and 267 pregnancies exposed to OAH (64.6% in the first trimester) and compared pregnancy outcome with that of 929 NTC. The rate of congenital anomalies did not differ among the groups [loratadine: 4/175 (2.3%), OAH: 10/247 (4.0%), NTC: 25/844 (3.0%), P =.553, relative risk (RR), 0.77; 95% confidence interval (CI), 0.27 to 2.19, (loratadine vs NTC); RR, 0.56; 95% CI, 0.18 to 1.77, (loratadine vs OAH)]. The rate did not differ between those exposed to antihistamines in the first trimester and the control patients [loratadine: 1/126 (0.8%), OAH: 7/146 (4.8%), NTC: 25/844 (3.0%), P =.152, RR, 0.27; 95% CI, 0.04 to 1.94, (loratadine vs NTC); RR, 0.17; 95% CI, 0.02 to 1.33, (loratadine vs OAH)]. CONCLUSIONS: This study on the use of loratadine in human pregnancy suggests that this agent does not represent a major teratogenic risk. The study was powered to find a 3-fold increase in the overall rate of major anomalies.
Asunto(s)
Anomalías Inducidas por Medicamentos/epidemiología , Antagonistas de los Receptores Histamínicos/efectos adversos , Antagonistas de los Receptores Histamínicos H1 no Sedantes/efectos adversos , Loratadina/efectos adversos , Adulto , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Israel/epidemiología , Embarazo , Resultado del Embarazo , Trimestres del EmbarazoRESUMEN
OBJECTIVE: Mebendazole is an anthelmintic that is commonly needed in women of reproductive age. Its use in pregnancy is a reason for concern for women and their health care providers. The purpose of this study was to examine the fetal safety of mebendazole. STUDY DESIGN: The Israeli Teratogen Information Service prospectively collected and followed 192 pregnancies exposed to mebendazole in pregnancy, 71.5% of whom had first-trimester exposure. Pregnancy outcome was compared with that of a matched control group, who were counseled for nonteratogenic exposure. RESULTS: There was no increase in the rate of major malformations between the groups (5/150 pregnancies [3.3%; mebendazole] vs 3/175 pregnancies [1.7%; nonteratogenic control subjects]; P =.478). There was a higher rate of elective terminations of pregnancy in the exposed group compared with the control group (22/192 pregnancies [11.5%; mebendazole] vs 3/192 pregnancies [1.6% [nonteratogenic control subjects]; P =.000). CONCLUSION: This study suggests that mebendazole does not represent a major teratogenic risk in humans when it is used in the doses that are used commonly for pinworm (Enterobius vermicularis) infestation.
Asunto(s)
Anomalías Inducidas por Medicamentos/epidemiología , Antinematodos/efectos adversos , Mebendazol/efectos adversos , Resultado del Embarazo , Aborto Inducido/estadística & datos numéricos , Adulto , Peso al Nacer , Estudios de Cohortes , Enterobiasis/tratamiento farmacológico , Femenino , Edad Gestacional , Humanos , Intercambio Materno-Fetal , Mebendazol/administración & dosificación , Embarazo , Estudios Prospectivos , Factores de RiesgoRESUMEN
Nausea and vomiting are very common during pregnancy, mainly throughout the first trimester. Metoclopramide is a dopamine receptor blocking drug that is commonly used to treat nausea and vomiting. The aim of this prospective study was to investigate the effect on the fetus of intrauterine exposure to metoclopramide. One hundred and seventy-five women who received metoclopramide and consulted 6 teratogen information centers in Israel, Italy, Brazil, and Canada were studied. Women exposed to metoclopramide were paired for age, smoking and alcohol consumption habits with women exposed to nonteratogens. Women in the metoclopramide group had a significantly higher rate of premature births (8.1%) as compared with the control group (2.4%) ( p = 0.02, relative risk = 3.37, 95% confidence interval 1.12-10.12). Rates of major malformations in the metoclopramide group (4.4%) did not differ from controls (4.8%) ( p = 0.84, relative risk = 0.91, 95% confidence interval 0.34-2.45). According to our findings, metoclopramide use during the first trimester of pregnancy does not appear to be associated with an increased risk of malformations, spontaneous abortions, or decreased birth weight, however, larger studies are needed to confirm these observations.