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1.
Environ Health ; 23(1): 51, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831396

RESUMO

BACKGROUND: Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies have been successful in reducing rates of spina bifida, some areas continue to be at higher risk because of chemical exposures. Bangladesh has high arsenic exposures through contaminated drinking water and high rates of spina bifida. This study examines the relationships between mother's arsenic exposure, folic acid, and spina bifida risk in Bangladesh. METHODS: We conducted a hospital-based case-control study at the National Institute of Neurosciences & Hospital (NINS&H) in Dhaka, Bangladesh, between December 2016 and December 2022. Cases were infants under age one year with spina bifida and further classified by a neurosurgeon and imaging. Controls were drawn from children seen at NINS&H and nearby Dhaka Shishu Hospital. Mothers reported folic acid use during pregnancy, and we assessed folate status with serum assays. Arsenic exposure was estimated in drinking water using graphite furnace atomic absorption spectrophotometry (GF-AAS) and in toenails using inductively coupled plasma mass spectrometry (ICP-MS). We used logistic regression to examine the associations between arsenic and spina bifida. We used stratified models to examine the associations between folic acid and spina bifida at different levels of arsenic exposure. RESULTS: We evaluated data from 294 cases of spina bifida and 163 controls. We did not find a main effect of mother's arsenic exposure on spina bifida risk. However, in stratified analyses, folic acid use was associated with lower odds of spina bifida (adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.25-1.00, p = 0.05) among women with toenail arsenic concentrations below the median value of 0.46 µg/g, and no association was seen among mothers with toenail arsenic concentrations higher than 0.46 µg/g (adjusted OR: 1.09, 95% CI: 0.52-2.29, p = 0.82). CONCLUSIONS: Mother's arsenic exposure modified the protective association of folic acid with spina bifida. Increased surveillance and additional preventive strategies, such as folic acid fortification and reduction of arsenic, are needed in areas of high arsenic exposure.


Assuntos
Arsênio , Ácido Fólico , Disrafismo Espinal , Humanos , Ácido Fólico/uso terapêutico , Bangladesh/epidemiologia , Disrafismo Espinal/prevenção & controle , Disrafismo Espinal/epidemiologia , Disrafismo Espinal/induzido quimicamente , Estudos de Casos e Controles , Feminino , Arsênio/análise , Lactente , Masculino , Adulto , Recém-Nascido , Gravidez , Poluentes Químicos da Água/análise , Exposição Materna , Adulto Jovem , Água Potável/química , Água Potável/análise
2.
Front Public Health ; 9: 695192, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368062

RESUMO

Limited studies have focused on the impact of ambient air pollution on spina bifida. A population-based case-control study was conducted in Liaoning Province, China to assess the associations between maternal PM10 exposures in various exposure windows and spina bifida risk. Data on spina bifida cases born between 2010 and 2015 were available from the Maternal and Child Health Certificate Registry of Liaoning Province. Controls were a random sample of healthy livebirths without any birth defects delivered in the selected five cities during 2010-2015. Ambient air monitoring data for PM10 were obtained from 75 monitoring stations in Liaoning Province. The multivariable logistic regression models were established to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI). We further performed sensitivity analyses by using three propensity score methods. A total of 749 spina bifida cases and 7,950 controls were included. After adjusting for potential confounders, spina bifida was associated with a 10 µg/m3 increment in PM10 during the first trimester of pregnancy (adjusted OR = 1.06, 95% CI: 1.00-1.12) and the 3 months before pregnancy (adjusted OR = 1.12, 95% CI: 1.06-1.19). The adjusted ORs in the final model for the highest vs. the lowest quartile were 1.51 (95% CI: 1.04-2.19) for PM10 during the first trimester of pregnancy and 2.01 (95% CI: 1.43-2.81) for PM10 during the 3 months before pregnancy. Positive associations were found between PM10 exposures during the single month exposure windows and spina bifida. Sensitivity analyses based on two propensity score methods largely reported similar positive associations. Our findings support the evidence that maternal PM10 exposure increases the risk of spina bifida in offspring. Further, validation with a prospective design and a more accurate exposure assessment is warranted.


Assuntos
Poluição do Ar , Disrafismo Espinal , Poluição do Ar/efeitos adversos , Estudos de Casos e Controles , Criança , Feminino , Humanos , Material Particulado/efeitos adversos , Gravidez , Estudos Prospectivos , Disrafismo Espinal/induzido quimicamente
4.
Drug Saf ; 41(3): 303-311, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29185237

RESUMO

INTRODUCTION: When a new drug enters the market, its full array of side effects remains to be defined. Current surveillance approaches targeting these effects remain largely reactive. There is a need for development of methods to predict specific safety events that should be sought for a given new drug during development and postmarketing activities. OBJECTIVE: We present here a safety signal identification approach applied to a new set of drug entities, inhibitors of the serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9). METHODS: Using phenome-wide association study (PheWAS) methods, we analyzed available genotype and clinical data from 29,722 patients, leveraging the known effects of changes in PCSK9 to identify novel phenotypes in which this protein and its inhibitors may have impact. RESULTS: PheWAS revealed a significantly reduced risk of hypercholesterolemia (odds ratio [OR] 0.68, p = 7.6 × 10-4) in association with a known loss-of-function variant in PCSK9, R46L. Similarly, laboratory data indicated significantly reduced beta mean low-density lipoprotein cholesterol (- 14.47 mg/dL, p = 2.58 × 10-23) in individuals carrying the R46L variant. The R46L variant was also associated with an increased risk of spina bifida (OR 5.90, p = 2.7 × 10-4), suggesting that further investigation of potential connections between inhibition of PCSK9 and neural tube defects may be warranted. CONCLUSION: This novel methodology provides an opportunity to put in place new mechanisms to assess the safety and long-term tolerability of PCSK9 inhibitors specifically, and other new agents in general, as they move into human testing and expanded clinical use.


Assuntos
Inibidores Enzimáticos/efeitos adversos , Inibidores de PCSK9 , Disrafismo Espinal/induzido quimicamente , LDL-Colesterol/metabolismo , Inibidores Enzimáticos/uso terapêutico , Feminino , Genótipo , Humanos , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/genética , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Vigilância de Produtos Comercializados/métodos , Fatores de Risco , Disrafismo Espinal/genética
5.
J Clin Psychopharmacol ; 38(1): 7-10, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29215383

RESUMO

PURPOSE/BACKGROUND: High risks of neural tube defects and other teratogenic effects are associated with exposure in early pregnancy to some anticonvulsants, including in women with bipolar disorder. METHODS/PROCEDURES: Based on a semistructured review of recent literature, we summarized findings pertaining to this topic. FINDINGS/RESULTS: Valproate and carbamazepine are commonly used empirically (off-label) for putative long-term mood-stabilizing effects. Both anticonvulsants have high risks of teratogenic effects during pregnancy. Risks of neural tube defects (especially spina bifida) and other major malformations are especially great with valproate and can arise even before pregnancy is diagnosed. Standard supplementation of folic acid during pregnancy can reduce risk of spontaneous spina bifida, but not that associated with valproate or carbamazepine. In contrast, lamotrigine has regulatory approval for long-term use in bipolar disorder and appears not to have teratogenic effects in humans. IMPLICATIONS/CONCLUSIONS: Lack of protective effects against anticonvulsant-associated neural tube defects by folic acid supplements in anticipation of and during pregnancy is not widely recognized. This limitation and high risks of neural tube and other major teratogenic effects, especially of valproate, indicate the need for great caution in the use of valproate and carbamazepine to treat bipolar disorder in women of child-bearing age.


Assuntos
Antimaníacos/efeitos adversos , Ácido Fólico/administração & dosagem , Defeitos do Tubo Neural/prevenção & controle , Disrafismo Espinal/prevenção & controle , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Antimaníacos/administração & dosagem , Transtorno Bipolar/tratamento farmacológico , Carbamazepina/administração & dosagem , Carbamazepina/efeitos adversos , Suplementos Nutricionais , Feminino , Humanos , Lamotrigina , Defeitos do Tubo Neural/induzido quimicamente , Gravidez , Complicações na Gravidez/tratamento farmacológico , Disrafismo Espinal/induzido quimicamente , Triazinas/administração & dosagem , Triazinas/efeitos adversos , Ácido Valproico/administração & dosagem , Ácido Valproico/efeitos adversos
6.
Birth Defects Res A Clin Mol Teratol ; 106(11): 963-971, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27891778

RESUMO

BACKGROUND: Because of persistent concerns over the association between pesticides and spina bifida, we examined the role of paternal and combined parental occupational pesticide exposures in spina bifida in offspring using data from a large population-based study of birth defects. METHODS: Occupational information from fathers of 291 spina bifida cases and 2745 unaffected live born control infants with estimated dates of delivery from 1997 to 2002 were collected by means of maternal report. Two expert industrial hygienists estimated exposure intensity and frequency to insecticides, herbicides, and fungicides. Multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for exposure to any pesticide and to any class of pesticide (yes/no; and by median), and exposure to combinations of pesticides (yes/no) and risk of spina bifida. Adjusted odds ratios were also estimated by parent exposed to pesticides (neither, mother only, father only, both parents). RESULTS: Joint parental occupational pesticide exposure was positively associated with spina bifida (aOR, 1.5; 95% CI, 0.9-2.4) when compared with infants with neither maternal nor paternal exposures; a similar association was not observed when only one parent was exposed. There was a suggested positive association between combined paternal insecticide and fungicide exposures and spina bifida (aOR, 1.5; 95% CI, 0.8-2.8), however, nearly all other aORs were close to unity. CONCLUSION: Overall, there was little evidence paternal occupational pesticide exposure was associated with spina bifida. However, the small numbers make it difficult to precisely evaluate the role of pesticide classes, individually and in combination. Birth Defects Research (Part A) 106:963-971, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Exposição Materna/efeitos adversos , Exposição Ocupacional/efeitos adversos , Exposição Paterna/efeitos adversos , Praguicidas/toxicidade , Disrafismo Espinal/epidemiologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Disrafismo Espinal/induzido quimicamente
7.
Am J Epidemiol ; 182(8): 675-84, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26424074

RESUMO

Nitrosatable drugs (NSDs) can, in the presence of nitrosating agents and highly acidic conditions, form N-nitroso compounds that have been found to be teratogenic in animal models. Using data from the Slone Epidemiology Center Birth Defects Study collected from 1998 to 2012, we compared maternal periconceptional NSD use between 334 neural tube defect cases and 7,619 nonmalformed controls. We categorized NSDs according to their functional group (secondary amine, tertiary amine, and amide). With logistic regression models, we estimated adjusted odds ratios and 95% confidence intervals. Neural tube defect risk was associated with maternal periconceptional use of secondary (adjusted odds ratio (aOR) = 1.7, 95% confidence interval (CI): 1.1, 2.4) and tertiary (aOR = 1.7, 95% CI: 1.2, 2.5) amines; an association was observed for amides, but the 95% confidence interval included the null (aOR = 1.4, 95% CI: 0.7, 2.5). Within the secondary amine group, elevated adjusted odds ratios were observed for 3 drugs but were null for the remaining medications. Increases in risk were observed for both strata of folic acid intake (<400 µg/day, ≥400 µg/day), with a slightly higher risk in the ≥400-µg/day stratum. Our findings support previously reported positive associations between neural tube defects and periconceptional exposure to NSDs containing a secondary or tertiary amine or amide.


Assuntos
Amidas/efeitos adversos , Aminas/efeitos adversos , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/epidemiologia , Compostos Nitrosos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Amidas/administração & dosagem , Aminas/administração & dosagem , Canadá/epidemiologia , Estudos de Casos e Controles , Medicina Baseada em Evidências , Feminino , Humanos , Incidência , Gravidez , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Prevalência , Medição de Risco , Fatores de Risco , Disrafismo Espinal/induzido quimicamente , Disrafismo Espinal/epidemiologia , Estados Unidos/epidemiologia
8.
Environ Health ; 14: 16, 2015 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-25971584

RESUMO

BACKGROUND: While there is evidence that maternal exposure to benzene is associated with spina bifida in offspring, to our knowledge there have been no assessments to evaluate the role of multiple hazardous air pollutants (HAPs) simultaneously on the risk of this relatively common birth defect. In the current study, we evaluated the association between maternal exposure to HAPs identified by the United States Environmental Protection Agency (U.S. EPA) and spina bifida in offspring using hierarchical Bayesian modeling that includes Stochastic Search Variable Selection (SSVS). METHODS: The Texas Birth Defects Registry provided data on spina bifida cases delivered between 1999 and 2004. The control group was a random sample of unaffected live births, frequency matched to cases on year of birth. Census tract-level estimates of annual HAP levels were obtained from the U.S. EPA's 1999 Assessment System for Population Exposure Nationwide. Using the distribution among controls, exposure was categorized as high exposure (>95(th) percentile), medium exposure (5(th)-95(th) percentile), and low exposure (<5(th) percentile, reference). We used hierarchical Bayesian logistic regression models with SSVS to evaluate the association between HAPs and spina bifida by computing an odds ratio (OR) for each HAP using the posterior mean, and a 95% credible interval (CI) using the 2.5(th) and 97.5(th) quantiles of the posterior samples. Based on previous assessments, any pollutant with a Bayes factor greater than 1 was selected for inclusion in a final model. RESULTS: Twenty-five HAPs were selected in the final analysis to represent "bins" of highly correlated HAPs (ρ > 0.80). We identified two out of 25 HAPs with a Bayes factor greater than 1: quinoline (ORhigh = 2.06, 95% CI: 1.11-3.87, Bayes factor = 1.01) and trichloroethylene (ORmedium = 2.00, 95% CI: 1.14-3.61, Bayes factor = 3.79). CONCLUSIONS: Overall there is evidence that quinoline and trichloroethylene may be significant contributors to the risk of spina bifida. Additionally, the use of Bayesian hierarchical models with SSVS is an alternative approach in the evaluation of multiple environmental pollutants on disease risk. This approach can be easily extended to environmental exposures, where novel approaches are needed in the context of multi-pollutant modeling.


Assuntos
Poluentes Atmosféricos/toxicidade , Substâncias Perigosas/toxicidade , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Disrafismo Espinal/epidemiologia , Adolescente , Adulto , Teorema de Bayes , Monitoramento Ambiental , Feminino , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Razão de Chances , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Prevalência , Disrafismo Espinal/induzido quimicamente , Texas/epidemiologia , Adulto Jovem
9.
J Pediatr Surg ; 50(1): 69-73, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25598096

RESUMO

PURPOSE: We sought to determine whether simple intra-amniotic delivery of concentrated amniotic mesenchymal stem cells (afMSCs) may elicit prenatal coverage of experimental spina bifida. METHODS: Time-dated pregnant Sprague-Dawley dams (n=24) exposed to retinoic acid for the induction of fetal neural tube defects were divided in three groups. Group I had no further manipulations. Groups II and III received volume-matched intra-amniotic injections of either saline (Group II) or a suspension of syngeneic afMSCs labeled with green fluorescent protein (Group III) in all fetuses (n=202) on gestational day 17 (term=21-22 days). Animals were killed before term. Statistical comparisons were by ANOVA (P<0.05). RESULTS: Of 165 fetuses viable at euthanasia, a spina bifida was present in 58% (96/165), with no significant differences in defect dimension across the groups (P=0.19). However, variable degrees of coverage of the defect by a rudimentary skin confirmed histologically were only present in Group III (P<0.001), in which donor afMSCs were documented, with no differences between Groups I and II (P=0.98). CONCLUSIONS: Amniotic mesenchymal stem cells can induce partial or complete coverage of experimental spina bifida after concentrated intra-amniotic injection. Trans-amniotic stem cell therapy (TRASCET) may become a practical option in the prenatal management of spina bifida.


Assuntos
Líquido Amniótico/citologia , Transplante de Células-Tronco Mesenquimais , Disrafismo Espinal/terapia , Âmnio , Animais , Modelos Animais de Doenças , Feminino , Injeções/métodos , Células-Tronco Mesenquimais/patologia , Gravidez , Ratos Sprague-Dawley , Disrafismo Espinal/induzido quimicamente , Disrafismo Espinal/patologia
10.
Birth Defects Res A Clin Mol Teratol ; 100(1): 22-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24382678

RESUMO

UNLABELLED: Maternal tea consumption was reported to increase the risk of fetal neural tube defects (NTDs). Catechol-O-methyltransferase (COMT) may be involved in the metabolism of polyphenolic methylation of tea, thus influence the risk of fetal NTDs. METHODS: A total of 576 fetuses or newborns with NTDs and 594 healthy newborns were included in the case-control study. Information on maternal tea consumption, sociodemographic characteristics, reproductive history, and related behavior was collected through face-to-face interviews. Maternal blood samples were collected to examine polymorphisms in COMT, and the possible interaction of COMT and tea consumption was analyzed. RESULTS: After controlling for potential confounders, homozygotes of rs737865 showed an elevated risk for total NTDs (odds ratio [OR] = 2.04, 95% confidence interval [CI], 1.24-3.35) and for the anencephaly subtype (OR = 1.99, 95% CI, 1.17-3.39). The CC genotype of rs4633 was positively associated with the overall risk of NTDs (OR = 3.66, 95% CI, 1.05-12.83). Heterozygotes for rs4680 were associated with a decreased risk of spina bifida (OR = 0.71, 95% CI, 0.51-0.98). The COMT rs4680 A allele was negatively related with the risk of spina bifida, with adjusted OR = 0.64 (95% CI, 0.45-0.89). An interaction between tea consumption (1 to 2 cups/day) and the rs4680AA/AG genotype was found in the spina bifida subtype (Pinteraction = .08). CONCLUSION: Several COMT variants were associated with elevated risk of NTDs in a Chinese population. Maternal tea consumption may be associated with an increased risk for fetal NTDs in genetically susceptible subgroups.


Assuntos
Anencefalia/genética , Catecol O-Metiltransferase/genética , Defeitos do Tubo Neural/genética , Polimorfismo de Nucleotídeo Único , Disrafismo Espinal/genética , Chá/efeitos adversos , Adulto , Anencefalia/induzido quimicamente , Anencefalia/enzimologia , Estudos de Casos e Controles , Catecol O-Metiltransferase/metabolismo , China , Feminino , Feto , Predisposição Genética para Doença , Humanos , Masculino , Exposição Materna/efeitos adversos , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/enzimologia , Razão de Chances , Polifenóis/toxicidade , Fatores de Risco , População Rural , Disrafismo Espinal/induzido quimicamente , Disrafismo Espinal/enzimologia
11.
Neurology ; 81(11): 999-1003, 2013 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-23911758

RESUMO

OBJECTIVE: To study the relationships between maternal valproate dose in pregnancy and the pattern of various fetal malformations. METHODS: Analysis of data in the Australian Register of Antiepileptic Drugs in Pregnancy collected from 1999 to 2012. The specific type of fetal malformation in offspring exposed to valproate in utero was correlated with the dose of valproate taken by the mother in the first trimester. RESULTS: Compared with other malformations, the mean dose of valproate taken during the first trimester was higher in mothers whose offspring had spina bifida (2,000 ± 707 vs 1,257 ± 918 mg/d) and hypospadias (2,417 ± 1,320 vs 1,235 ± 715 mg/d) (both p < 0.05). The overall mean maternal valproate dosage taken by women in the Register decreased over the last 5 years of the study period. This was paralleled by a statistically significant decrease in the rate of occurrence of spina bifida and hypospadias, but not other malformations. CONCLUSIONS: Human fetal malformations associated with valproate exposure during pregnancy do not all seem to bear the same quantitative relationship to drug dose, and reduction in valproate dose in earlier pregnancy is likely to offer greater dividends in protecting against spina bifida and hypospadias than against other types of fetal malformations.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anticonvulsivantes/efeitos adversos , Doenças Fetais/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ácido Valproico/efeitos adversos , Anormalidades Induzidas por Medicamentos/epidemiologia , Áustria/epidemiologia , Relação Dose-Resposta a Droga , Epilepsia/tratamento farmacológico , Feminino , Humanos , Hipospadia/induzido quimicamente , Hipospadia/epidemiologia , Modelos Logísticos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Disrafismo Espinal/induzido quimicamente , Disrafismo Espinal/epidemiologia
12.
Birth Defects Res A Clin Mol Teratol ; 94(8): 620-5, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22847955

RESUMO

The use of prescription opioids is becoming an increasing problem among women of reproductive age. More than half of pregnancies are unintended; therefore, many first-trimester exposures to opioids occur before pregnancy confirmation. Studies are limited about the fetal risks to opioid exposure in early pregnancy. One large study demonstrated an increased risk of certain heart defects and spina bifida with first-trimester exposure to opioids. It is important to counsel women whose fetuses were exposed to opioids in early pregnancy about the potential risks, encourage them to cease using opioids or seek alternative treatments when appropriate, and use the lowest effective dose when opioid treatment is to be continued. It is also valuable to screen for anatomic abnormalities such as neural tube and cardiac defects with available maternal serum testing and ultrasound imaging in the early second trimester. Birth Defects Research (Part A) 94:620-625, 2012. © 2012 Wiley Periodicals, Inc.


Assuntos
Analgésicos Opioides/efeitos adversos , Aconselhamento , Cardiopatias Congênitas/prevenção & controle , Disrafismo Espinal/prevenção & controle , Analgésicos Opioides/administração & dosagem , Esquema de Medicação , Feminino , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/diagnóstico , Humanos , Recém-Nascido , Exposição Materna , Gravidez , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Segundo Trimestre da Gravidez/efeitos dos fármacos , Diagnóstico Pré-Natal , Disrafismo Espinal/induzido quimicamente , Disrafismo Espinal/diagnóstico
13.
Occup Environ Med ; 69(7): 493-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22447643

RESUMO

OBJECTIVES: Though toxicological experiments demonstrate the teratogenicity of organic solvents in animal models, epidemiologic studies have reported inconsistent results. Using data from the population-based National Birth Defects Prevention Study, the authors examined the relation between maternal occupational exposure to aromatic solvents, chlorinated solvents and Stoddard solvent during early pregnancy and neural tube defects (NTDs) and orofacial clefts (OFCs). METHODS: Cases of NTDs (anencephaly, spina bifida and encephalocoele) and OFCs (cleft lip ± cleft palate and cleft palate alone) delivered between 1997 and 2002 were identified by birth defect surveillance registries in eight states; non-malformed control infants were selected using birth certificates or hospital records. Maternal solvent exposure was estimated by industrial hygienist review of self-reported occupational histories in combination with a literature-derived exposure database. ORs and 95% CIs for the association between solvent class and each birth defect group and component phenotype were estimated using multivariable logistic regression, adjusting for maternal age, race/ethnicity, education, pre-pregnancy body mass index, folic acid supplement use and smoking. RESULTS: The prevalence of exposure to any solvent among mothers of NTD cases (n = 511), OFC cases (n = 1163) and controls (n = 2977) was 13.1%, 9.6% and 8.2%, respectively. Exposure to chlorinated solvents was associated with increased odds of NTDs (OR = 1.96, CI 1.34 to 2.87), especially spina bifida (OR = 2.26, CI 1.44 to 3.53). No solvent class was strongly associated with OFCs in these data. CONCLUSIONS: The findings suggest that maternal occupational exposure to chlorinated solvents during early pregnancy is positively associated with the prevalence of NTDs in offspring.


Assuntos
Hidrocarbonetos Clorados/efeitos adversos , Exposição Materna/efeitos adversos , Anormalidades da Boca/etiologia , Defeitos do Tubo Neural/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Complicações na Gravidez/induzido quimicamente , Solventes/efeitos adversos , Adolescente , Adulto , Anencefalia/induzido quimicamente , Anencefalia/epidemiologia , Intervalos de Confiança , Encefalocele/induzido quimicamente , Encefalocele/epidemiologia , Feminino , Humanos , Hidrocarbonetos/efeitos adversos , Hidrocarbonetos Aromáticos/efeitos adversos , Recém-Nascido , Modelos Logísticos , Defeitos do Tubo Neural/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Razão de Chances , Gravidez , Complicações na Gravidez/epidemiologia , Prevalência , Fatores de Risco , Autorrelato , Disrafismo Espinal/induzido quimicamente , Disrafismo Espinal/epidemiologia , Adulto Jovem
14.
Am J Med Genet C Semin Med Genet ; 157C(3): 234-46, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21766433

RESUMO

Selected antiepileptic drugs (AEDs) increase the risk of birth defects. To assess the impact of influencing AED prescribing practices on spina bifida and cleft palate we searched the literature for estimates of the association between valproic acid or carbamazepine use during pregnancy and these defects and summarized the associations using meta-analyses. We estimated distributions of the prevalence of valproic acid and carbamazepine use among women of childbearing age based on analyses of four data sets. We estimated the attributable fractions and the number of children born with each defect that could be prevented annually in the United States if valproic acid and carbamazepine were not used during pregnancy. The summary odds ratio estimate for the association between valproic acid and spina bifida was 11.9 (95% uncertainty interval (UI): 4.0-21.2); for valproic acid and cleft palate 5.8 (95% UI: 3.3-9.5); for carbamazepine and spina bifida 3.6 (95% UI: 1.3-7.8); and for carbamazepine and cleft palate 2.4 (95% UI: 1.1-4.5) in the United States. Approximately 40 infants (95% UI: 10-100) with spina bifida and 35 infants (95% UI: 10-70) with cleft palate could be born without these defects each year if valproic acid were not used during pregnancy; 5 infants (95% UI: 0-15) with spina bifida and 5 infants (95% UI: 0-15) with cleft palate could be born without these defects each year if carbamazepine were not used during pregnancy. This modeling approach could be extended to other medications to estimate the impact of translating pharmacoepidemiologic data to evidence-based prenatal care practice.


Assuntos
Anticonvulsivantes/uso terapêutico , Fissura Palatina/epidemiologia , Disrafismo Espinal/epidemiologia , Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Carbamazepina/uso terapêutico , Fissura Palatina/induzido quimicamente , Fissura Palatina/prevenção & controle , Feminino , Humanos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Cuidado Pré-Natal , Prevalência , Disrafismo Espinal/induzido quimicamente , Disrafismo Espinal/prevenção & controle , Estados Unidos , Ácido Valproico/efeitos adversos , Ácido Valproico/uso terapêutico
16.
Fed Regist ; 76(16): 4245-50, 2011 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-21275190

RESUMO

This document adopts as a final rule the Department of Veterans Affairs' (VA) proposal to amend VA adjudication, medical, and vocational rehabilitation and employment regulations to incorporate relevant provisions of the Veterans Benefits Act of 2003. Specifically, this document amends VA regulations regarding herbicide exposure of certain veterans who served in or near the Korean demilitarized zone and regulations regarding spina bifida in their children. It also amends VA's medical regulations by correcting the Health Administration Center's hand-delivery address.


Assuntos
Ácido 2,4,5-Triclorofenoxiacético/toxicidade , Ácido 2,4-Diclorofenoxiacético/toxicidade , Anormalidades Induzidas por Medicamentos , Anormalidades Congênitas/etiologia , Desfolhantes Químicos/toxicidade , Exposição Ambiental/legislação & jurisprudência , Herbicidas/toxicidade , Cobertura do Seguro/legislação & jurisprudência , Exposição Ocupacional/efeitos adversos , Exposição Paterna , Dibenzodioxinas Policloradas/toxicidade , Disrafismo Espinal/induzido quimicamente , Veteranos/legislação & jurisprudência , Humanos , Revisão da Utilização de Seguros/legislação & jurisprudência , Guerra da Coreia , Masculino , Exposição Ocupacional/legislação & jurisprudência , República da Coreia , Estados Unidos
17.
Am J Obstet Gynecol ; 204(4): 314.e1-11, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21345403

RESUMO

OBJECTIVE: We examined whether maternal opioid treatment between 1 month before pregnancy and the first trimester was associated with birth defects. STUDY DESIGN: The National Birth Defects Prevention Study (1997 through 2005) is an ongoing population-based case-control study. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIS) for birth defects categories with at least 200 case infants or at least 4 exposed case infants. RESULTS: Therapeutic opioid use was reported by 2.6% of 17,449 case mothers and 2.0% of 6701 control mothers. Treatment was statistically significantly associated with conoventricular septal defects (OR, 2.7; 95% CI, 1.1-6.3), atrioventricular septal defects (OR, 2.0; 95% CI, 1.2-3.6), hypoplastic left heart syndrome (OR, 2.4; 95% CI, 1.4-4.1), spina bifida (OR, 2.0; 95% CI, 1.3-3.2), or gastroschisis (OR, 1.8; 95% CI, 1.1-2.9) in infants. CONCLUSION: Consistent with some previous investigations, our study shows an association between early pregnancy maternal opioid analgesic treatment and certain birth defects. This information should be considered by women and their physicians who are making treatment decisions during pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos , Analgésicos Opioides/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Adulto , Analgésicos Opioides/administração & dosagem , Câmara Anterior/anormalidades , Estudos de Casos e Controles , Codeína/administração & dosagem , Codeína/efeitos adversos , Feminino , Gastrosquise/induzido quimicamente , Gastrosquise/epidemiologia , Glaucoma/induzido quimicamente , Glaucoma/epidemiologia , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/epidemiologia , Humanos , Hidrocefalia/induzido quimicamente , Hidrocefalia/epidemiologia , Hidrocodona/administração & dosagem , Hidrocodona/efeitos adversos , Recém-Nascido , Meperidina/administração & dosagem , Meperidina/efeitos adversos , Análise Multivariada , Oxicodona/administração & dosagem , Oxicodona/efeitos adversos , Gravidez , Primeiro Trimestre da Gravidez , Estenose da Valva Pulmonar/induzido quimicamente , Estenose da Valva Pulmonar/epidemiologia , Disrafismo Espinal/induzido quimicamente , Disrafismo Espinal/epidemiologia
18.
Pediatr Neurosurg ; 47(3): 194-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22301488

RESUMO

BACKGROUND: Spina bifida is a long-known disease arising from the incomplete fusion of the caudal neuropore in the first month of intrauterine life. It is thought to have a multifactorial etiology, the most important of which is folic acid deficiency. In evaluating its etiology, the role of antifolate agents like antimalarial drugs is rarely given a strong mention. METHODS/PATIENTS: This is a 44-month prospective study of consecutive cases of spina bifida cystica presenting to the Neurosurgery Unit of Nnamdi Azikiwe University Teaching Hospital, Nnewi, South-East Nigeria. Data collection was with a structured proforma from presentation, and collation done with Microsoft Excel broadsheet and data analysis with SPSS and χ2 test. RESULTS: A total of 41 cases of spina bifida were attended to within the period, with 92.7% cases of spina bifida cystica. Most presented by >12-24 months, with a consistent history of maternal ingestion of antimalarial drugs during the first trimester of pregnancy. CONCLUSION: Spina bifida cystica was diagnosed mostly in children whose mothers ingested antimalarial drugs during the first trimester of gestation. There may be a need to critically evaluate the contribution of antimalarial drugs to the etiopathogenesis of this malformation and develop safer antimalarial treatment in pregnancy.


Assuntos
Antimaláricos/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Disrafismo Espinal/induzido quimicamente , Disrafismo Espinal/epidemiologia , Pré-Escolar , Feminino , Deficiência de Ácido Fólico/induzido quimicamente , Deficiência de Ácido Fólico/epidemiologia , Deficiência de Ácido Fólico/etiologia , Humanos , Lactente , Recém-Nascido , Masculino , Nigéria/epidemiologia , Gravidez , Primeiro Trimestre da Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Estudos Prospectivos , Fatores de Risco , Disrafismo Espinal/etiologia
19.
Eur J Epidemiol ; 25(1): 37-44, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19894129

RESUMO

The objective of this study is to conduct a meta-analysis of published and unpublished studies that examine the association between Agent Orange (AO) exposure and the risk of spina bifida. Relevant studies were identified through a computerized literature search of Medline and Embase from 1966 to 2008; a review of the reference list of retrieved articles and conference proceedings; and by contacting researchers for unpublished studies. Both fixed-effects and random-effects models were used to pool the results of individual studies. The Cochrane Q test and index of heterogeneity (I(2)) were used to evaluate heterogeneity, and a funnel plot and Egger's test were used to evaluate publication bias. Seven studies, including two Vietnamese and five non-Vietnamese studies, involving 330 cases and 134,884 non-cases were included in the meta-analysis. The overall relative risk (RR) for spina bifida associated with paternal exposure to AO was 2.02 (95% confidence interval [CI]: 1.48-2.74), with no statistical evidence of heterogeneity across studies. Non-Vietnamese studies showed a slightly higher summary RR (RR = 2.22; 95% CI: 1.38-3.56) than Vietnamese studies (RR = 1.92 95% CI: 1.29-2.86). When analyzed separately, the overall association was statistically significant for the three case-control studies (Summary Odds Ratio = 2.25, 95% CI: 1.31-3.86) and the cross sectional study (RR = 1.97, 95% CI: 1.31-2.96), but not for the three cohort studies (RR: 2.11; 95% CI: 0.78-5.73). Paternal exposure to AO appears to be associated with a statistically increased risk of spina bifida.


Assuntos
Ácido 2,4,5-Triclorofenoxiacético/toxicidade , Ácido 2,4-Diclorofenoxiacético/toxicidade , Anormalidades Induzidas por Medicamentos , Desfolhantes Químicos/toxicidade , Exposição Ocupacional/efeitos adversos , Exposição Paterna , Dibenzodioxinas Policloradas/toxicidade , Disrafismo Espinal/induzido quimicamente , Agente Laranja , Anormalidades Congênitas/etiologia , Humanos , Masculino , Medição de Risco , Vietnã
20.
Alcohol Clin Exp Res ; 32(8): 1361-71, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18565153

RESUMO

INTRODUCTION: Prenatal alcohol exposure via maternal liquid diet consumption by C57BL/6 (B6) mice causes conspicuous midline neural tube deficit (dysraphia) and disruption of genesis and development of serotonin (5-HT) neurons in the raphe nuclei, together with brain growth retardation. The current study tested the hypothesis that concurrent treatment with either an activity-dependent neurotrophic factor (ADNF) agonist peptide [SALLRSIPA, (SAL)] or an activity-dependent neurotrophic protein (ADNP) agonist peptide [NAPVSIPQ, (NAP)] would protect against these alcohol-induced deficits in brain development. METHODS: Timed-pregnant B6 dams consumed alcohol from embryonic day 7 (E7, before the onset of neurulation) until E15. Fetuses were obtained on E15 and brain sections processed for 5-HT immunocytochemistry, for evaluation of morphologic development of the brainstem raphe and its 5-HT neurons. Additional groups were treated either with SAL or NAP daily from E7 to E15 to assess the potential protective effects of these peptides. Measures of incomplete occlusion of the ventral canal and the frequency and extent of the openings in the rhombencephalon were obtained to assess fetal dysraphia. Counts of 5-HT-immunostained neurons were also obtained in the rostral and caudal raphe. RESULTS: Prenatal alcohol exposure resulted in abnormal openings along the midline and delayed closure of ventral canal in the brainstem. This dysraphia was associated with reductions in the number of 5-HT neurons both in the rostral raphe nuclei (that gives rise to ascending 5-HT projections) and in the caudal raphe (that gives rise to the descending 5-HT projections). Concurrent treatment of the alcohol-consuming dams with SAL prevented dysraphia and protected against the alcohol-induced reductions in 5-HT neurons in both the rostral and caudal raphe. NAP was less effective in protecting against dysraphia and did not protect against 5-HT loss in the rostral raphe, but did protect against loss in the caudal raphe. CONCLUSIONS: These findings further support the potential usefulness of these peptides for therapeutic interventions in pregnancies at risk for alcohol-induced developmental deficits. Notably, the ascending 5-HT projections of the rostral raphe have profound effects in regulating forebrain development and function, and the descending 5-HT projections of the caudal raphe are critical for regulating respiration. Protection of the rostral 5-HT-system may help prevent structural and functional deficits linked to abnormal forebrain development, and protection of the caudal systems may also reduce the increased risk for sudden infant death syndrome associated with prenatal alcohol exposure.


Assuntos
Depressores do Sistema Nervoso Central/efeitos adversos , Etanol/efeitos adversos , Proteínas de Homeodomínio/agonistas , Proteínas do Tecido Nervoso/agonistas , Defeitos do Tubo Neural/prevenção & controle , Fragmentos de Peptídeos/uso terapêutico , Animais , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/metabolismo , Depressores do Sistema Nervoso Central/farmacologia , Modelos Animais de Doenças , Etanol/farmacologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Degeneração Neural/induzido quimicamente , Degeneração Neural/prevenção & controle , Defeitos do Tubo Neural/induzido quimicamente , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuropeptídeos , Oligopeptídeos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Lesões Pré-Natais/induzido quimicamente , Lesões Pré-Natais/prevenção & controle , Respiração/efeitos dos fármacos , Serotonina/metabolismo , Disrafismo Espinal/induzido quimicamente , Disrafismo Espinal/prevenção & controle
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