Early prenatal exposure to air pollutants and congenital heart disease: a nested case-control study

BACKGROUND@#Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease.@*METHODS@#The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease.@*RESULTS@#A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m3 increase of gestational exposure to PM2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1st-2nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O3 exposure during the 1st week and SO2 exposure during 6th-7th weeks in the first trimester, while no significant findings for other air pollutants.@*CONCLUSIONS@#This study highlighted that gestational exposure to PM2.5, O3, and SO2 had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.

Abordagem metabolômica no estudo de exposição gestacional à fumaça de Cannabis sativa em cobaias / A metabolomics study of gestational exposure to smoke of Cannabis sativa in mice

Os estudos de metabolômica ganham importância a cada dia, por ajudarem a explicar processos biológicos em situações normais (fisiológicas) ou patológicas. Oferecem uma nova visão sobre o impacto funcional da expressão gênica, complementando os estudos de sequenciamento gênico, que negligenciam o impacto da exposição ao meio ambiente na etiologia de doenças. A metabolômica tem sido aplicada na toxicologia, mostrando que o perfil metabólico comparativo de duas situações, controle e teste, pode desempenhar um papel importante na descoberta e validação de biomarcadores, além de contribuir para o entendimento e consequente interpretação dos mecanismos de ação tóxica de xenobióticos. Este projeto de pesquisa tem por objetivo utilizar uma abordagem metabolômica para avaliar o impacto de alterações metabólicas no cérebro da prole de camundongos, ocorridas após exposição (via inalação) à fumaça decorrente da queima de maconha (Cannabis sativa). Fêmeas gestantes foram expostas a doses diárias de Cannabis sativa ou ar filtrado durante todo o período gestacional. Após o nascimento, os filhotes machos ao atingirem a idade para o desmame, considerado como fase adolescente, foram separados de suas respectivas mães e expostos à Cannabis sativa ou ar filtrado por mais 60 dias. As amostras de cérebro da prole foram submetidas a análises por cromatografia em fase gasosa acoplada a espectrometria de massas (CG-MS) numa abordagem metabolômica global (untargeted metabolomics). Os perfis metabólicos dos cérebros dos animais expostos (grupo teste) foram comparados com os obtidos na análise do grupo controle (não expostos), sendo identificados os metabólitos discriminadores candidatos. Estavam alterados os metabólitos: isoleucina, uréia, leucina, GABA, ácido succínico, ácido fumárico, serina, treonina, creatinina, ácido glutâmico, ácido acetilaspártico, glicerol -1 -fosfato, ácido ascórbico, tirosina, ácido cítrico, adenina, hipoxantina, inosina e uracila. A partir dos resultados apresentados, pode-se observar, que tanto a exposição gestacional à Cannabis sativa, quanto a exposição da prole na fase adolescente, provocam alterações metabólicas importantes. Os metabólitos significativamente alterados estão envolvidos no ciclo do ácido tricarboxílico, responsável pela respiração mitocondrial, na produção de energia, atuam na biossíntese de aminoácidos, glicólise, estresse oxidativo, podendo alterar o desenvolvimento e maturação do cérebro. Os resultados são preliminares, mas contribuem para o melhor entendimento dos mecanismos toxicológicos envolvidos na exposição crônica causada por essa droga, contribuindo para a prevenção e diagnóstico de danos no desenvolvimento fetal e adolescente

Metabolomics studies gain importance each day because they help explain biological processes in normal (physiological) or pathological situations. They provide a new insight into the functional impact of environmental gene expression, complementing gene sequencing studies that neglect the impact of environmental exposure on the etiology of diseases. Metabolomics has been applied in toxicology, showing that the comparative metabolic profile of two situations, control and test, can play an important role in the discovery and validation of biomarkers, in addition to contributing to the understanding and interpretation of the toxic action mechanisms of xenobiotics. This research project aims to use a metabolomic approach to evaluate the impact of metabolic changes in the brain of the offspring of mice, which occurred after exposure (via inhalation) to the smoke from the burning Cannabis sativa. Pregnant females were exposed to daily doses of Cannabis sativa or filtered air throughout the gestational period. After birth, male offspring were reached adolescents weaning age were separated from their respective mothers and exposed to Cannabis sativa or to the filtrate for another 60 days. Offspring brain samples were analyzed by gas chromatography coupled to mass spectrometry (GC-MS) in a global metabolomic approach (non-target metabolomics). Metabolic profiles of the exposed animals brains (test group) were compared with those obtained in the control group (non-exposed), and the candidate discriminant metabolites were identified. The metabolites were altered: isoleucine, urea, leucine, GABA, succinic acid, fumaric acid, serine, threonine, creatine, glutamic acid, acetyl aspartic acid, glycerol-1-phosphate, ascorbic acid, tyrosine, citric acid, adenine, hypoxanthine, inosine and uracil were altered. From the results presented, it can be observed that both the gestational exposure in Cannabis sativa and the exposure of the adolescent phase exposure, induced important metabolic alterations. Significantly altered metabolites are involved in the tricarboxylic acid, which are responsible for mitochondrial respiration, in energy production, act at the amino acid biosynthesis, glycolysis, oxidative stress, which may alter the development and maturation of the brain. The results are preliminary but contribute to a better understanding of the mechanisms of toxicity and of fetal and adolescent infection

Effect of pregnancy complications and gestational exposure to toxic chemical on birth defect:a systematic ;evaluation / 中国基层医药

Objective To investigate the impact of pregnancy complications and gestational exposure to toxic chemical on birth defect,to provide scientific basis for effective intervention measures.Methods 11 studies were included,the quality evaluation and information extraction were carried out on the studies according to include and exclude standard.3 248 examples in case group and 5 722 examples in control group.Fixed or random effects model was used according to heterogeneity test results,and the combined result was analyzed by Chi -square test.The publi-cation bias of the studies was also evaluated.Results The combined results of single factor analysis of pregnancy complications was 1.074(0.926 -1.222),showed that pregnancy complications were risk factors of birth defects.The combined results of single factor and multiple factors analysis of gestational exposure to toxic chemical were 1.426 (1.147 -1.704),1.421(1.174 -1.668),also showed that gestational exposure to toxic chemical was a risk factor of birth defects.Conclusion Pregnancy complications and gestational exposure to toxic chemical are risk factors of birth defects,this targeted provides reference to birth defects prevention.

Developmental and neurobehavioural toxicity study of arsenic on rats following gestational exposure.

To characterize developmental and behavioral alterations induced by arsenic exposure, Albino rats were exposed to arsenic (0, 1.5, 3.0 and 4.5 mg/kg/day/po) from gestation day 8 to till parturition and the offspring were observed over the first 3 postnatal weeks, until they were weaned on post-natal day (PND) 21. Once the pups were delivered (PND0), the treatment was discontinued. All pups were assessed for physical development, reflex development, strength and motor coordination from standard neurobehavioural developmental test batteries beginning on PND1. Gestational administration of arsenic at tested dose levels, showed no significant changes in the day of appearance of eye opening, startle reflex, negative geotaxis and spontaneous alteration performance in comparison to the control group. The number of live fetuses, mean fetal body weight and percentages of resorptions or malformations per litter were not affected by arsenic exposure. No treatment-related malformations or developmental variations were noted at any exposure level, suggesting that arsenic exposure at this dose level did not adversely affect behavioural endpoints of developmental toxicity.

Investigación de cocaína y marihuana en meconio de neonatos atendidos en un hospital público: primera experiencia realizada en la ciudad de Córdoba, Argentina / Screening of cocaine and marijuana in meconium of newborns from a public hospital of city of Córdoba, Argentina

Se investigaron cocaína y marihuana en meconio de neonatos nacidos en la Maternidad Provincial de la Ciudad de Córdoba y se relacionaron los resultados con las semanas de gestación y los pesos al nacer. Las determinaciones se realizaron utilizando inmunoensayo y cromatografía gaseosa-espectrometría de masas. Se analizaron 48 muestras de meconio recolectadas durante un año (2007-2008). De los 48 meconios analizados, 17 correspondieron a neonatos masculinos y 31 a neonatos femeninos. Se procesaron en paralelo 15 muestras de meconio como controles normales (niños no expuestos a drogas) seleccionados por historia clínica y controles prenatales. De las 48 muestras de meconio 13 fueron positivas para cocaína y/o marihuana. El peso y las semanas degestación de los neonatos cuyas muestras fueron positivas se compararon frente a un grupo control normal, hallándose mayores diferencias estadísticamente significativas (α=0,05 – p<0,0001) en relación a los pesos al nacer. Estos resultados, a pesar del reducido número de casos analizados, resaltan la importancia de la investigación de drogas de abuso en meconio, lo que permite confirmar el uso de drogas por parte de la madre durante el período gestacional temprano, y de ese modo interpretar las alteraciones (déficit de peso) observadas en el neonato al nacer, atribuibles al consumo de drogas durante la gestación.

We investigated cocaine and marijuana in meconium of newborns attended at the Hospital Materno Provincial of Córdoba City and the results were correlated with birthweight and weeks of pregnancy. The samples were analyzed using immunoassay (FPIA) and gas chromatography-mass spectrometry (GC-MS) for confirmation. Forty eight samples of meconium were collected during one year period (2007-2008). Of the 48 samples screened, 17 correspond to masculine sex and 31 to feminine. Fifteen samples of meconium from normal newborns (newborns not exposed to drugs) selected by maternal self report, pregnancy controls were processed as control group. The results obtained in 48 samples of meconium showed 13 cases tested positive for cocaine and/or marijuana. Birth weight and weeks of gestation of newborn with positive sample results were compared with a control group. A statistically significant difference (α= 0.05 - p<0.0001) was found in relation to birth weight. Although these results arise from a small number of samples, these data have relevance in public health and show the importance of the screening of drugs of abuse in meconium to confirm use in mothers during pregnancy and to interpret the alterations observed in the newborn after delivery as consequence of drug use in prenatal period.