RESUMEN
Human leukocyte antigen (HLA) genes are very informative in population genetics studies and their variability has been widely used to reconstruct the history of geographic and/or demographic expansions of human populations. The characterization of HLA diversity at the population level is also fundamental in clinical studies, particularly for bone marrow transplantation programs. In this study, we investigated the HLA molecular variation in Rio Grande do Sul, South Brazil, in order to identify possible regional differences across this state. More than 97,000 bone marrow donors were typed at the HLA- A, -B and -DRB1 loci and analyzed by considering two kinds of subdivisions based on both self-identified ethnicity and place of residence: (a) the official geographic subdivision defined by the Brazilian Institute of Geography and Statistics and (b) known information about the colonization history of the state. HLA allele and haplotype frequencies were estimated and compared among the defined subgroups. The results indicate a lack of correlation between genetic variation and geography and thus no clear HLA genetic structure based on geographic criteria. On the other hand, major differences were observed regarding ethnicity. In addition, local populations from Rio Grande do Sul were found to be genetically similar to their corresponding parental European populations from Germany, Italy and Portugal, as documented by historical data. Overall, this study provides a thorough characterization of the HLA genetic variation in Rio Grande do Sul and a better understanding of its demographic history, being most useful for the development of more efficient strategies in bone marrow donors' recruitment.
RESUMEN
Some cases of recurrent first trimester miscarriage have a thrombotic etiology. The aim of this study was to investigate the prevalence of the most common thrombophilic mutations - factor V (FV) Leiden G1691A (FVL), prothrombin (FII) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T - in women with recurrent miscarriages. In this case-control study, we included 137 women with two or more consecutive first-trimester miscarriages (£12 weeks of gestation) and 100 healthy women with no history of pregnancy loss, and with at least one living child. DNA was extracted from the patient samples, and the relevant genes (FVL, FII, and MTHFR) were amplified by PCR, followed by restriction fragment length polymorphism, to assess the polymorphisms in these genes. The allelic frequencies of polymorphisms were not significantly different between the case and control groups. Polymorphisms in the MTHFR, FVL, and FII genes were not associated with recurrent miscarriage during the first trimester of pregnancy in Brazilian women (P = 0.479; P = 0.491 and P = 0.107, respectively). However, the etiologic identification of genetic factors is important for genetic counseling.
Asunto(s)
Aborto Habitual/genética , Factor V/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo de Longitud del Fragmento de Restricción , Protrombina/genética , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Humanos , EmbarazoRESUMEN
In 2015 an unprecedented increase of reports of newborns with microcephaly in Brazil made news headlines around the world. A possible etiological association with prenatal maternal infection by Zika virus (ZIKV) was suggested based on temporal and geographic distribution of ZIKV infection and the subsequent increase in the reports of microcephaly cases. Here we discuss ZIKV as a new human teratogen, with comments on potential treatment options.
Asunto(s)
Microcefalia/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Infección por el Virus Zika/complicaciones , Animales , Brasil/epidemiología , Femenino , Humanos , Recién Nacido , Microcefalia/virología , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/terapiaRESUMEN
Controversies about Mendelian segregation and CAG expansion (CAGexp) instabilities during meiosis in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) need clarification. Additional evidence about these issues was obtained from the cohort of all SCA3/MJD individuals living in South Brazil. A survey was carried out to update information registered since 2001. Deaths were checked with the Public Information System, and data was made anonymous. Anticipation and delta-CAGexp from parent-offspring pairs, and delta-CAGexp between siblings were obtained. One hundred and fifty-nine families (94% of the entire registry) were retrieved, comprising 3725 living individuals as of 2015, 625 of these being symptomatic. Minimal prevalence was 6:100,000. Carriers of a CAGexp represented 65.6% of sibs in the genotyped offspring (p < 0.001). Median instability was larger among paternal than maternal transmissions, and instabilities correlated with anticipation (r = 0.38; p = 0.001). Age of the parent correlated to delta-CAGexp among 115 direct parent-offspring CAGexp transmissions (ρ = 0.23, p = 0.014). In 98 additional kindreds, the delta-CAGexp between 269 siblings correlated with their delta-of-age (ρ = 0.27, p < 0.0001). SCA3/MJD was associated with a segregation distortion favoring the expanded allele in our cohort. Instability of expansion during meiosis was weakly influenced by the age of the transmitting parent at the time of conception.
Asunto(s)
Ataxina-3/genética , Inestabilidad Genómica , Patrón de Herencia , Enfermedad de Machado-Joseph/genética , Proteínas Represoras/genética , Expansión de Repetición de Trinucleótido , Adolescente , Adulto , Factores de Edad , Edad de Inicio , Alelos , Enfermedades Asintomáticas , Segregación Cromosómica , Femenino , Frecuencia de los Genes , Heterocigoto , Humanos , Enfermedad de Machado-Joseph/patología , Masculino , Meiosis , Linaje , Índice de Severidad de la Enfermedad , Factores Sexuales , HermanosRESUMEN
Congenital aniridia is a rare genetic disorder characterized by varying degrees of iris hypoplasia that are associated with additional ocular abnormalities. More than 90% of the causal mutations identified are found in the PAX6 gene, a transcription factor of critical importance in the process of neurogenesis and ocular development. Here, we investigate clinical, molecular, and craniofacial features of a large Brazilian family with congenital aniridia. Among the 56 eyes evaluated, phenotype variation encompassed bilateral total aniridia to mild iris defects with extensive variation between eyes of the same individual. PAX6 molecular screening indicated a heterozygous splice mutation (c.141 + 1G>A). Thus, we hypothesize that this splicing event may cause variation in the expression of the wild-type transcript, which may lead to the observed variation in phenotype. Affected individuals were more brachycephalic, even though their face height and cephalic circumference were not significantly different when compared to those of non-affected relatives. From this, we infer that the head shape of affected subjects may also be a result of the PAX6 splice-site mutation. Our data summarize the clinical variability associated with the ocular phenotype in a large family with aniridia, and help shed light on the role of PAX6 in neurocranial development.
Asunto(s)
Aniridia/genética , Aniridia/patología , Anomalías Craneofaciales/patología , Anomalías del Ojo/patología , Proteínas del Ojo/genética , Proteínas de Homeodominio/genética , Factores de Transcripción Paired Box/genética , Fenotipo , Proteínas Represoras/genética , Adolescente , Adulto , Anciano , Análisis de Varianza , Secuencia de Bases , Brasil , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación/genética , Factor de Transcripción PAX6 , Linaje , Análisis de Secuencia de ADNRESUMEN
Polymorphisms of hormone receptor genes have been linked to modifications in reproductive factors and to an increased risk of breast cancer (BC). In the present study, we have determined the allelic and genotypic frequencies of the ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms and investigated their relationship with mammographic density, body mass index (BMI) and other risk factors for BC. A consecutive and unselected sample of 750 Brazilian BC-unaffected women enrolled in a mammography screening program was recruited. The distribution of PGR PROGINS genotypic frequencies was 72.5, 25.5 and 2.0% for A1A1, A1A2 and A2A2, respectively, which was equivalent to that encountered in other studies with healthy women. The distribution of ERα genotypes was: ERα-397 PvuII C/T: 32.3% TT, 47.5% TC, and 20.2% CC; ERα-351 XbaI A/G: 46.3% AA, 41.7% AG and 12.0% GG. ERα haplotypes were 53.5% PX, 14.3% Px, 0.3% pX, and 32.0% px. These were significantly different from most previously published reports worldwide (P < 0.05). Overall, the PGR PROGINS genotypes A2A2 and A1A2 were associated with fatty and moderately fatty breast tissue. The same genotypes were also associated with a high BMI in postmenopausal women. In addition, the ERα-351 XbaI GG genotype was associated with menarche ≥12 years (P = 0.02). ERα and PGR polymorphisms have a phenotypic effect and may play an important role in BC risk determination. Finally, if confirmed in BC patients, these associations could have important implications for mammographic screening and strategies and may be helpful to identify women at higher risk for the disease.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/genética , Desoxirribonucleasas de Localización Especificada Tipo II/genética , Receptor alfa de Estrógeno/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético/genética , Receptores de Progesterona/genética , Índice de Masa Corporal , Brasil , Neoplasias de la Mama/diagnóstico , Frecuencia de los Genes , Genotipo , Glándulas Mamarias Humanas/anomalías , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND: Cândido Godói (CG) is a small town in South Brazil, which has the highest prevalence of twin births in Brazil. Recently, a number of studies have shown that p53 plays an important role in reproduction through blastocyst implantation and intra utero embryo survival. Thus, gene polymorphisms in the p53 pathway were investigated in this population. METHODS: Single nucleotide polymorphisms from five genes in the p53 pathway were investigated, as well as background characteristics of 42 mothers of twins (cases) and 101 mothers of singletons (controls), all residents from CG. RESULTS: Mothers of twins have higher number of pregnancies and higher frequencies of P72 allele at TP53 and T allele at MDM4 genes compared with controls. Logistic regression shows that both TP53 and number of pregnancies maintained their association with twinning (P =0.004 and P =0.002, respectively), with TP53 having a higher odds ratio than number of pregnancies (2.73 versus 1.70, respectively). No interactive effect between TP53 and MDM4 (P =0.966) is observed. As expected, mothers of twins have three times more cases of cancer in their first-degree relatives than control mothers (P =0.011). CONCLUSIONS: Our results suggest that the P72 allele of TP53 is a strong risk factor for twinning in CG, while the number of pregnancies and the T allele at MDM4 may represent weaker risk factors. These two alleles are associated with infertility, but the anti-apoptotic effect of low levels of p53 in general, and of the P72 allele in particular, may play a role after implantation, enhancing the chance for a double pregnancy to succeed to term.
Asunto(s)
Fertilidad/genética , Fertilidad/fisiología , Genes p53 , Proteína p53 Supresora de Tumor/genética , Gemelos/genética , Adulto , Alelos , Blastocisto , Brasil , Estudios de Casos y Controles , Implantación del Embrión , Femenino , Humanos , Infertilidad , Oportunidad Relativa , Polimorfismo Genético , Embarazo , Prevalencia , Factores de RiesgoRESUMEN
Polymorphisms of hormone receptor genes have been linked to modifications in reproductive factors and to an increased risk of breast cancer (BC). In the present study, we have determined the allelic and genotypic frequencies of the ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms and investigated their relationship with mammographic density, body mass index (BMI) and other risk factors for BC. A consecutive and unselected sample of 750 Brazilian BC-unaffected women enrolled in a mammography screening program was recruited. The distribution of PGR PROGINS genotypic frequencies was 72.5, 25.5 and 2.0% for A1A1, A1A2 and A2A2, respectively, which was equivalent to that encountered in other studies with healthy women. The distribution of ERα genotypes was: ERα-397 PvuII C/T: 32.3% TT, 47.5% TC, and 20.2% CC; ERα-351 XbaI A/G: 46.3% AA, 41.7% AG and 12.0% GG. ERα haplotypes were 53.5% PX, 14.3% Px, 0.3% pX, and 32.0% px. These were significantly different from most previously published reports worldwide (P < 0.05). Overall, the PGR PROGINS genotypes A2A2 and A1A2 were associated with fatty and moderately fatty breast tissue. The same genotypes were also associated with a high BMI in postmenopausal women. In addition, the ERα-351 XbaI GG genotype was associated with menarche ≥ 12 years (P = 0.02). ERα and PGR polymorphisms have a phenotypic effect and may play an important role in BC risk determination. Finally, if confirmed in BC patients, these associations could have important implications for mammographic screening and strategies and may be helpful to identify women at higher risk for the disease.
Asunto(s)
Neoplasias de la Mama/genética , Desoxirribonucleasas de Localización Especificada Tipo II/genética , Receptor alfa de Estrógeno/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético/genética , Receptores de Progesterona/genética , Adulto , Anciano , Índice de Masa Corporal , Brasil , Densidad de la Mama , Neoplasias de la Mama/diagnóstico , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Glándulas Mamarias Humanas/anomalías , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
Several studies have identified the single nucleotide polymorphism STK15 F31I as a low-penetrance risk allele for breast cancer, but its prevalence and risk association in the Brazilian population have not been determined. The goal of this study was to identify the frequency of this polymorphism in the Brazilian setting. Considering the high degree of admixture of our population, it is of fundamental importance to validate the results already reported in the literature and also to verify the relationship between this variant and breast cancer risk. A total of 750 women without breast cancer were genotyped using the TaqMan PCR assay for STK15 F31I polymorphism. Clinical information was obtained from review of the medical records and mammographic density from the images obtained using the BI-RADS System. The estimated risk of developing cancer was calculated according to the Gail model. The genotypic frequencies observed in this study were 4.5, 38.7, and 56.6 percent, respectively, for the STK15 F31I AA, AT and TT genotypes. The AT and AA genotypes were encountered significantly more often in premenopausal women with moderately dense, dense and heterogeneously dense breast tissue (P = 0.023). In addition, the presence of the TT genotype was significantly associated with age at menarche ≥12 years (P = 0.023). High mammographic density, associated with increased breast cancer risk, was encountered more frequently in premenopausal women with the risk genotypes STK15 F31I AA and AT. The genotypic frequencies observed in our Brazilian sample were similar to those described in other predominantly European populations.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/genética , Mamografía , Polimorfismo de Nucleótido Simple/genética , Proteínas Serina-Treonina Quinasas/genética , Neoplasias de la Mama/enzimología , Neoplasias de la Mama , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de RiesgoRESUMEN
Several studies have identified the single nucleotide polymorphism STK15 F31I as a low-penetrance risk allele for breast cancer, but its prevalence and risk association in the Brazilian population have not been determined. The goal of this study was to identify the frequency of this polymorphism in the Brazilian setting. Considering the high degree of admixture of our population, it is of fundamental importance to validate the results already reported in the literature and also to verify the relationship between this variant and breast cancer risk. A total of 750 women without breast cancer were genotyped using the TaqMan PCR assay for STK15 F31I polymorphism. Clinical information was obtained from review of the medical records and mammographic density from the images obtained using the BI-RADS System. The estimated risk of developing cancer was calculated according to the Gail model. The genotypic frequencies observed in this study were 4.5, 38.7, and 56.6%, respectively, for the STK15 F31I AA, AT and TT genotypes. The AT and AA genotypes were encountered significantly more often in premenopausal women with moderately dense, dense and heterogeneously dense breast tissue (P = 0.023). In addition, the presence of the TT genotype was significantly associated with age at menarche ≥12 years (P = 0.023). High mammographic density, associated with increased breast cancer risk, was encountered more frequently in premenopausal women with the risk genotypes STK15 F31I AA and AT. The genotypic frequencies observed in our Brazilian sample were similar to those described in other predominantly European populations.
Asunto(s)
Neoplasias de la Mama/genética , Mamografía , Polimorfismo de Nucleótido Simple/genética , Proteínas Serina-Treonina Quinasas/genética , Adulto , Anciano , Aurora Quinasa A , Aurora Quinasas , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/enzimología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de RiesgoRESUMEN
Non-syndromic cleft lip and palate (CL/P) occurs due to interaction between genetic and environmental factors. Abnormalities in homocysteine metabolism may play a role in its etiology due to polymorphisms in genes involved in this pathway. Because of the involvement of MTHFR, MTR and MTRR genes with folate metabolism and the evidence that maternal use of folic acid in early pregnancy reduces the risk for CL/P, we evaluated the influence of their polymorphisms on the etiology of CL/P through a case-control study. The analyses involved 114 non-syndromic phenotypically white children with clefts (case) and 110 mothers, and 100 non-affected (control) children and their mothers. The polymorphisms 677C>T of MTHFR, 2756A>G of MTR, and 66A>G of MTRR genes were analyzed by PCR-RFLP. Allelic frequencies did not differ from other studies conducted on white populations for MTHFR 677T allele (0.35) and for MTR 2756G allele (0.17), but MTRR 66G allele frequency (0.35) was lower than observed elsewhere. The genotypic distribution of the 677C>T polymorphisms under study did not show significant differences between CL/P patients, their mothers and controls. These results suggest that the alterations of folate metabolism related to these polymorphisms are not involved in clefting in the population under study.
Asunto(s)
5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , Labio Leporino/enzimología , Fisura del Paladar/enzimología , Ferredoxina-NADP Reductasa/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Labio Leporino/genética , Fisura del Paladar/genética , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Reacción en Cadena de la Polimerasa , Embarazo , Factores de RiesgoRESUMEN
Non-syndromic cleft lip and palate (CL/P) occurs due to interaction between genetic and environmental factors. Abnormalities in homocysteine metabolism may play a role in its etiology due to polymorphisms in genes involved in this pathway. Because of the involvement of MTHFR, MTR and MTRR genes with folate metabolism and the evidence that maternal use of folic acid in early pregnancy reduces the risk for CL/P, we evaluated the influence of their polymorphisms on the etiology of CL/P through a case-control study. The analyses involved 114 non-syndromic phenotypically white children with clefts (case) and 110 mothers, and 100 non-affected (control) children and their mothers. The polymorphisms 677C>T of MTHFR, 2756A>G of MTR, and 66A>G of MTRR genes were analyzed by PCR-RFLP. Allelic frequencies did not differ from other studies conducted on white populations for MTHFR 677T allele (0.35) and for MTR 2756G allele (0.17), but MTRR 66G allele frequency (0.35) was lower than observed elsewhere. The genotypic distribution of the 677C>T polymorphisms under study did not show significant differences between CL/P patients, their mothers and controls. These results suggest that the alterations of folate metabolism related to these polymorphisms are not involved in clefting in the population under study.
Asunto(s)
Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , /genética , Labio Leporino/enzimología , Fisura del Paladar/enzimología , Ferredoxina-NADP Reductasa/genética , /genética , Polimorfismo Genético , Estudios de Casos y Controles , Labio Leporino/genética , Fisura del Paladar/genética , Reacción en Cadena de la Polimerasa , Factores de RiesgoRESUMEN
The objective of the present study was to evaluate and quantify fetal risks involved in the administration of cancer chemotherapy during gestation, as well as to assess the long-term effects on the exposed children. In this retrospective, cohort study, we reviewed the records of women aged 15 to 45 years with a diagnosis of malignancy or benign tumors with malignant behavior at three reference services in the State of Rio Grande do Sul, Brazil, from 1990 to 1997. All patients with a diagnosis of pregnancy at any time during the course of the disease were selected, regardless of whether or not they received specific medication. Fetal outcomes of 14 pregnancies with chemotherapy exposure were compared to that of 15 control pregnancies in which these drugs were not used. Long-term follow-up of the exposed children was carried out. Fisher's exact test was used to compare the groups. Continuous variables were compared by the Wilcoxon-Mann-Whitney test. We found an increased rate of prematurity (6/8 vs 2/10; RR: 3.75; CI: 1.02-13.8; P = 0.03) in the exposed group. There was a trend to an increased fetal death rate (4/12 vs 0/10; P = 0.07) in the group exposed to chemotherapy. No malformations were detected in any child, which can be related to our small sample size as well as to the fact that most exposures occurred after the first trimester of pregnancy. Other larger, controlled studies are needed to establish the actual risk related to cancer chemotherapy during pregnancy
Asunto(s)
Humanos , Femenino , Embarazo , Recién Nacido , Adolescente , Adulto , Persona de Mediana Edad , Antineoplásicos , Muerte Fetal , Trabajo de Parto Prematuro , Complicaciones Neoplásicas del Embarazo , Anomalías Inducidas por Medicamentos , Aborto Espontáneo , Puntaje de Apgar , Estudios de Cohortes , Estudios de Seguimiento , Edad Gestacional , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The objective of the present study was to evaluate and quantify fetal risks involved in the administration of cancer chemotherapy during gestation, as well as to assess the long-term effects on the exposed children. In this retrospective, cohort study, we reviewed the records of women aged 15 to 45 years with a diagnosis of malignancy or benign tumors with malignant behavior at three reference services in the State of Rio Grande do Sul, Brazil, from 1990 to 1997. All patients with a diagnosis of pregnancy at any time during the course of the disease were selected, regardless of whether or not they received specific medication. Fetal outcomes of 14 pregnancies with chemotherapy exposure were compared to that of 15 control pregnancies in which these drugs were not used. Long-term follow-up of the exposed children was carried out. Fisher's exact test was used to compare the groups. Continuous variables were compared by the Wilcoxon-Mann-Whitney test. We found an increased rate of prematurity (6/8 vs 2/10; RR: 3.75; CI: 1.02-13.8; P = 0.03) in the exposed group. There was a trend to an increased fetal death rate (4/12 vs 0/10; P = 0.07) in the group exposed to chemotherapy. No malformations were detected in any child, which can be related to our small sample size as well as to the fact that most exposures occurred after the first trimester of pregnancy. Other larger, controlled studies are needed to establish the actual risk related to cancer chemotherapy during pregnancy.
Asunto(s)
Antineoplásicos/efectos adversos , Muerte Fetal/inducido químicamente , Trabajo de Parto Prematuro/inducido químicamente , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Anomalías Inducidas por Medicamentos , Aborto Espontáneo/inducido químicamente , Adolescente , Adulto , Puntaje de Apgar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Recién Nacido , Persona de Mediana Edad , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To assess the relationship between the environmental impact of coal mining and its effects in the reproductive health of populations living in small towns of Southern Brazil by studying the frequency of birth defects in newborns. METHODS: The assessment of potential reproductive hazards in the population was based on an evaluation of hospital records of 10,391 newborns within a 10-year-period (from 1985 to 1995). Eight major birth defects were selected and their frequencies at birth was analyzed and compared to observed frequencies registered by the Latin American Study of Congenital Malformation (ECLAMC). RESULTS/CONCLUSIONS: The results show no increase in the frequencies of the birth defects studied, and rule out the existence of an increased teratogenic risk in this region. It's noteworthy that the small number of children evaluated allows identifying tendencies that can only be confirmed in larger population studies.
Asunto(s)
Minas de Carbón , Anomalías Congénitas/epidemiología , Exposición a Riesgos Ambientales , Adulto , Brasil/epidemiología , Anomalías Congénitas/diagnóstico , Anomalías Congénitas/etiología , Femenino , Humanos , Recién Nacido , Masculino , Prevalencia , ReproducciónRESUMEN
Prenatal exposure to misoprostol has been associated with Moebius and limb defects. Vascular disruption has been proposed as the mechanism for these teratogenic effects. The present study is a multicenter, case-control study that was designed to compare the frequency of prenatal misoprostol use between mothers of Brazilian children diagnosed with vascular disruption defects and matched control mothers of children diagnosed with other types of defects. A total of 93 cases and 279 controls were recruited in eight participating centers. Prenatal exposure was identified in 32 infants diagnosed with vascular disruption defects (34.4%) compared with only 12 (4.3%) in the control group (P<0.0000001). Our data suggest that prenatal exposure to misoprostol is associated to the occurrence of vascular disruption defects in the newborns.