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1.
J Hazard Mater ; 424(Pt B): 127466, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34653865

RESUMO

The adverse effects of uranium exposure on human health are well-known; less is known, however, regarding its association with congenital malformations. We conducted a case-control study to examine the association between prenatal exposure to uranium and risk for fetal neural tube defects (NTDs) using the concentration of uranium in placental tissue as an exposure marker in 408 NTD cases and 593 healthy controls. Uranium concentration was quantified with an inductively coupled plasma mass spectrometer. The odds ratios of NTDs for uranium exposure levels, categorized into quartiles, were estimated using logistic regression. The median concentration of uranium in the NTD group (0.409 ng/g) was significantly higher than that in the control group (0.218 ng/g). The risk for NTDs increased 2.52-fold (95% CI, 1.85-3.45) for concentrations of uranium above the median value for all participants. After adjusting for confounders, the risk for NTDs increased 1.36-fold (95% CI, 1.25-6.17), 1.77-fold (95% CI, 1.09-2.85), and 3.60-fold (95% CI, 2.30-5.64) for the second, third, and fourth quartiles of uranium concentrations compared to the lowest quartile, respectively. Prenatal exposure to uranium is a risk factor for NTDs in this population. Prospective studies are needed to further validate this finding.

2.
China CDC Wkly ; 3(37): 773-777, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34594988

RESUMO

What is already known on this topic?: The prevalence of structural birth defects, especially neural tube defects, decreased after national folic acid (FA) supplementation initiation. What is added by this report?: The prevalence of orofacial clefts (OFCs) in five counties of Shanxi Province in northern China, including most subtypes except cleft palate, showed a downward trend in the past two decades. In this study, pre-perinatal prevalence increased due to earlier detection. What are the implications for public health practice?: Periconceptional supplementation with FA may contribute to the decline in OFCs prevalence, while the effect on the OFCs subtype needs further investigation. Continuing to advocate for earlier supplementation (3 months before conception) and increased supplementation frequency (daily consumption) could promote further reduction in the prevalence of OFCs. Specific surveillance of this effect in the era of universal three-child policy is warranted.

3.
China CDC Wkly ; 3(37): 778-782, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34594989

RESUMO

What is already known about this topic?: Passive smoking during pregnancy, which is prevalent in China, has been reported to be associated with an increased risk for neural tube defects (NTDs) in five counties of Shanxi Province in northern China. What is added by this report?: After 4 years since the implementation of the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) in China, 59.4% of mothers of NTDs cases and 29.4% of mothers of healthy controls reported passive smoking during the periconceptional period. The association between periconceptional passive smoking and an increased risk for NTDs remains in the study population. What are the implications for public health practice?: It's urgent to take measures to prevent passive smoking among pregnant women to minimize the harmful effects on offspring.

4.
J Pediatr ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34508748

RESUMO

OBJECTIVE: To determine the effects of maternal periconceptional supplementation with folic acid or multiple micronutrients containing folic acid on the prevention of fetal congenital heart defects (CHDs). STUDY DESIGN: Data were drawn from a Prenatal Health Care System and a Birth Defects Surveillance System in a district of Beijing, China. A total of 63 969 singleton births, live or stillborn, 308 CHDs among them, during 2013 to 2018 were included. Associations between different patterns of supplementation and risk for total CHDs or main types of CHDs were evaluated with risk ratios (RRs). RESULTS: For folic acid or multiple micronutrients containing folic acid users compared with nonusers, the adjusted RRs (ARRs) for total CHDs, critical CHD, and ventricular septal defect (VSD) were 0.60 (95% CI, 0.44-0.83), 0.41 (95% CI, 0.26-0.67), and 0.47 (95% CI, 0.30-0.74), respectively. When we compared multiple micronutrients containing folic acid users with folic acid users, the ARRs were 0.84 (95% CI, 0.66-1.09), 0.64 (95% CI, 0.41-1.00), and 0.94 (95% CI, 0.63-1.41) for total CHDs, critical CHD, and VSD, respectively. We also found that, compared with supplementation initiated after conception, supplementation initiated before conception was associated with a lower risk for CHDs: the ARRs were 0.68 (95% CI, 0.48-0.95) for total CHDs and 0.26 (95% CI, 0.10-0.71) for critical CHD, but 1.08 (95% CI, 0.63-1.83) for VSD. CONCLUSIONS: Maternal periconceptional supplementation with folic acid or multiple micronutrients containing folic acid seems to decrease the risk for CHDs, especially critical CHD, in offspring. Supplementation confers a greater protective effect when it is initiated before conception. We did not find any difference between folic acid and multiple micronutrients containing folic acid in terms of preventing CHDs.

5.
Chemosphere ; 284: 131387, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34217934

RESUMO

Aluminum (Al)1 is ubiquitously present in the environment, and human exposure to Al is common. Al has been reported to be involved in various human diseases and adverse pregnancy outcomes, including neural tube defects (NTDs). This study aimed to examine the association between prenatal Al exposure and the risk for NTDs using Al concentrations in maternal serum and placental tissue. The subjects were recruited from six counties/cities in the Shanxi province of northern China from 2003 to 2016. Al concentrations in both types of specimens were assessed using inductively coupled plasma-mass spectrometry. In the maternal serum cohort (200 cases and 400 controls), compared to the lowest tertile concentration of Al, the highest Al tertile was associated with 2.42-fold (95% confidence interval, 1.23-4.87) increased risk after adjustment for confounding factors. In the placental tissue cohort (408 cases and 593 controls), the highest tertile of Al also tended to be associated with an elevated risk for NTDs [adjusted odds ratio, 1.60 (0.94-2.70)]. When analyzed by NTD subtypes, the highest Al tertile was associated with an increased risk for anencephaly in both cohorts after adjustment for confounders [odds ratio, 1.97 (1.15-3.48) in the maternal serum cohort; odds ratio, 4.75 (2.01-12.00) in the placental tissue cohort]. Taken together, using concentrations of Al in maternal serum and placental tissue as exposure markers, we found that prenatal exposure to higher levels of Al is a risk factor for fetal NTDs, especially for the anencephaly subtype.


Assuntos
Alumínio , Defeitos do Tubo Neural , Feminino , Feto , Humanos , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/epidemiologia , Razão de Chances , Placenta , Gravidez
7.
Paediatr Perinat Epidemiol ; 35(6): 645-653, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34060120

RESUMO

BACKGROUND: Associations between the periconceptional folic acid only (FAO) or multiple micronutrients containing folic acid (MMFA) supplementation and risk for limb defects are inconsistent. OBJECTIVE: To explore the association between periconceptional folic acid supplements use and risk for limb defects, including clubfoot, polydactyly, syndactyly, and limb deficiencies. METHODS: Data were derived from a cohort based on a pregnancy registry in a district of Beijing, China, from 2013 to 2018. Information on maternal periconceptional FAO and MMFA supplementation was collected via face-to-face interviews at first trimester. Pregnancy outcomes including limb defects were ascertained in livebirths, stillbirths, and elective pregnancy terminations and were recorded into the system. Propensity score methods were used to adjust for potential confounders. RESULTS: A total of 63 969 women with a singleton delivery were included. The overall prevalence of limb defects was 47.5 per 10 000 (n = 63 969) singleton deliveries. Decreased prevalence of limb defects was found among FAO/MMFA users compared with women who did not take supplements (nonusers) (46.1 vs. 61.9 per 10 000 births, adjusted risk ratio [RR] 0.80, 95% confidence interval [CI] 0.56, 1.12). Compared with nonusers (n = 6462, 10.2%), women who took either FAO (n = 26 567, 42.0%) or MMFA (n = 30 259, 47.8%) had a lower risk for total clubfoot (RR 0.40, 95% CI 0.20, 0.84), and for isolated clubfoot (RR 0.41, 95% CI 0.17, 0.97). For other limb defects except clubfoot, FAO supplementation did not appear to be associated with reduced risk, while MMFA supplementation group had 30%-50% reduced risks for other limb defects. A lower risk for limb defects or isolated limb defects was found with MMFA supplementation when FAO supplementation was used as a control. CONCLUSIONS: Maternal periconceptional supplements with either FAO or MMFA had inverse association with clubfoot in offspring, and MMFA was associated with lower risk for isolated limb defects compared with FAO.

8.
Environ Health ; 20(1): 66, 2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090432

RESUMO

BACKGROUND: Prenatal exposure to heavy metals is implicated in the etiology of birth defects. We investigated whether concentrations of cadmium (Cd) and lead (Pb) in umbilical cord tissue are associated with risk for neural tube defects (NTDs) and whether selected genetic variants of the fetus modify their associations. METHODS: This study included 166 cases of NTD fetuses/newborns and 166 newborns without congenital malformations. Umbilical cord tissue was collected at birth or elective pregnancy termination. Cd and Pb concentrations were assessed by inductively coupled plasma-mass spectrometry, and 20 single-nucleotide polymorphisms (SNPs) in 9 genes were genotyped. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the risk for NTDs in association with metal concentrations or genotype using logistic regression. Multiplicative-scale interactions between the metals and genotypes on NTD risk were assessed with logistic regression, and additive-scale interactions were estimated with a non-linear mixed effects model. RESULTS: Higher concentrations of Cd were observed in the NTD group than in the control group, but no difference was found for Pb. Concentrations of Cd above the median level showed a risk effect, while the association between Pb and NTD risk was not significant in univariate analyses. The association of Cd was attenuated after adjusting for periconceptional folic acid supplementation. Fetuses with the AG and GG genotypes of rs4880 in SOD2 (superoxide dismutase 2) tended to have a lower risk, but fetuses with the CT and TT genotypes of rs1801133 in MTHFR (5,10-methylenetetrahydrofolatereductase) have a higher risk for NTDs when compared to their respective wild-type. rs4880 and Cd exhibited a multiplicative-scale interaction on NTD risk: the association between higher Cd and the risk for NTDs was increased by over fourfold in fetuses carrying the G allele [OR 4.43 (1.30-15.07)] compared to fetuses with the wild-type genotype. rs1801133 and Cd exposure showed an additive interaction, with a significant relative excess risk of interaction [RERI 0.64 (0.02-1.25)]. CONCLUSIONS: Prenatal exposure to Cd may be a risk factor for NTDs, and the risk effect may be enhanced in fetuses who carry the G allele of rs4880 in SOD2 and T allele of rs1801133 in MTHFR.


Assuntos
Cádmio/efeitos adversos , Poluentes Ambientais/efeitos adversos , Exposição Materna/efeitos adversos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Defeitos do Tubo Neural/genética , Superóxido Dismutase/genética , Adulto , Cádmio/análise , Estudos de Casos e Controles , China/epidemiologia , Poluentes Ambientais/análise , Feminino , Feto , Genótipo , Humanos , Recém-Nascido , Chumbo/análise , Troca Materno-Fetal , Defeitos do Tubo Neural/epidemiologia , Polimorfismo de Nucleotídeo Único , Gravidez
9.
Environ Pollut ; 286: 117249, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33975215

RESUMO

The relationship between heavy metal(loid)s exposure and oxidative stress damage is a matter of research interest. Our study aimed to investigate the distribution patterns of the nine heavy metal(loid)s in blood of pregnant women, including four toxic heavy metal(loid)s [arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg)] and five typical heavy metal(loid)s [manganese (Mn), cobalt (Co), copper (Cu), zinc (Zn), and selenium (Se)] in blood. Blood samples of 348 women were collected and their concentrations in the serum (sr) and blood cells (bc) were measured, as well as serum heme oxygenase-1 (HO-1) (an oxidative stress marker). Total blood (tb) concentrations of these metal(loid)s and serum-to-blood cell concentration ratios (sr/bc) were further calculated. We found Cu mainly accumulated in the serum compared to the blood cells with Cusr/bc = 2.30, whereas Co, Se, and As evenly distributed between these two fractions. Other metal(loid)s mainly concentrated in the blood cells. Cosr, Cusr, Cubc, Mnbc, Znbc, Cdbc, Cotb, Cutb, Mntb, Zntb, Cdtb, and Cusr/bc were negatively associated with serum HO-1, whereas Assr, Asbc, Astb, Znsr/bc, Cdsr/bc, and Hgsr/bc were positively, indicating of their potential toxicity. We concluded that the distribution patterns of blood heavy metal(loid)s, in particular for Cd, Hg and Zn, which either increased in serum or decreased in blood cells, might be associated with elevated serum oxidative stress, should be considered in environmental health assessments.


Assuntos
Arsênio , Metaloides , Metais Pesados , Arsênio/análise , Monitoramento Ambiental , Feminino , Heme Oxigenase-1 , Humanos , Metais Pesados/análise , Gravidez , Gestantes
10.
Environ Pollut ; 285: 117203, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33932758

RESUMO

Studies of the association between prenatal exposure to metal elements and risk for neural tube defects (NTDs) have produced inconsistent results. Little research has examined the joint effects and interactions of multiple elements. This study examined 273 women with NTD-affected pregnancies and 477 controls. Cadmium, cobalt, chromium, copper, iron, mercury, manganese, molybdenum, lead, and zinc were quantified in maternal serum. Single and mixed effects of these elements on NTD risk were evaluated with Bayesian kernel machine regression, and the effects of individual elements were validated using logistic regression. As a result, NTD risk increased with the concentration of the mixture of the 10 elements. NTD risk rose as the levels of the five toxic elements increased, with effect sizes larger than the overall analyses, but they decreased, albeit non-significantly, as the levels of the five essential elements increased. Lead and manganese showed risk effects on NTDs, with odds ratios (ORs) of 1.94 (1.76-2.13) and 1.25 (1.14-1.38), respectively, with the remaining nine elements remaining at their median. Molybdenum showed a protective effect against NTDs with an OR 0.87 (0.90-0.94). The single-element results were validated using logistic regression. In conclusion, NTD risk increased with concentrations of the five toxic elements, with lead and manganese being the major contributors. Essential elements showed protective effects against NTD risk.


Assuntos
Mercúrio , Defeitos do Tubo Neural , Teorema de Bayes , Estudos de Casos e Controles , Feminino , Feto , Humanos , Manganês , Defeitos do Tubo Neural/epidemiologia , Gravidez
11.
Ecotoxicol Environ Saf ; 217: 112228, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33892343

RESUMO

The relationship between maternal mercury (Hg) intake and the risk of spontaneous preterm birth (SPB) remains unclear. We conducted a nested case-control study from a prospective cohort in Shanxi Province, China, to explore their associations. In total, 126 pregnant women with SPB (cases) and 348 controls with term delivery were included. We measured the Hg concentrations in their serum (Hgs) and blood cell (Hgc) fractions and calculated the concentration ratio of Hg in serum to Hg in blood cells (Hgs/c). We found that only the Hgs/c in the case group was slightly higher than that in control group. The OR of Hgs/c associated with SPB risk was 1.57 [95%CI: 0.99-2.46] with adjusting confounders. After stratification by sampling time, the association above was only statistically significant in the first trimester. High Hgs/c may increase the risk of SPB in the first trimester among women with relatively low Hg exposure.


Assuntos
Poluentes Ambientais/sangue , Exposição Materna/estatística & dados numéricos , Mercúrio/sangue , Nascimento Prematuro/sangue , Adulto , Células Sanguíneas , Estudos de Casos e Controles , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos
12.
Front Cell Dev Biol ; 9: 641831, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748132

RESUMO

Background: Neural tube defects (NTDs) are among the most common and severe congenital defects in humans. Their genetic etiology is complex and remains poorly understood. The Mediator complex (MED) plays a vital role in neural tube development in animal models. However, no studies have yet examined the role of its human homolog in the etiology of NTDs. Methods: In this study, 48 pairs of neural lesion site and umbilical cord tissues from NTD and 21 case-parent trios were involved in screening for NTD-related somatic and germline de novo variants. A series of functional cell assays were performed. We generated a Med12 p.Arg1784Cys knock-in mouse using CRISPR/Cas9 technology to validate the human findings. Results: One somatic variant, MED12 p.Arg1782Cys, was identified in the lesion site tissue from an NTD fetus. This variant was absent in any other normal tissue from different germ layers of the same case. In 21 case-parent trios, one de novo stop-gain variant, MED13L p.Arg1760∗, was identified. Cellular functional studies showed that MED12 p.Arg1782Cys decreased MED12 protein level and affected the regulation of MED12 on the canonical-WNT signaling pathway. The Med12 p.Arg1784Cys knock-in mouse exhibited exencephaly and spina bifida. Conclusion: These findings provide strong evidence that functional variants of MED genes are associated with the etiology of some NTDs. We demonstrated a potentially important role for somatic variants in the occurrence of NTDs. Our study is the first study in which an NTD-related variant identified in humans was validated in mice using CRISPR/Cas9 technology.

13.
Environ Int ; 150: 106425, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33581418

RESUMO

OBJECTIVE: To examine the role of total mercury (T-Hg) in placenta as a biomarker of prenatal mercury (Hg) exposure and determine the association between prenatal Hg exposure and risk for neural tube defects (NTDs) in offspring. METHODS: Total Hg concentrations in placental tissue were detected in 408 NTD cases and 593 healthy controls enrolled in Shanxi province in northern China. Methylmercury (MeHg) and T-Hg were also detected in the umbilical cord of 147 NTD cases and 140 healthy controls. In addition, MeHg and T-Hg were detected in fetal kidney, liver, and brain tissues of 51 NTD cases. Spearman's rank correlation (rs) was used to evaluate the correlations between placental T-Hg and T-Hg in umbilical cord and fetal kidney, liver, and brain tissues. The Wilcoxon rank-sum test was used to compare T-Hg amounts between case and control groups. Logistic regression was used to examine the association between placental T-Hg and risk for NTDs. RESULTS: Placental T-Hg was significantly correlated with T-Hg in umbilical cord (rs = 0.479), kidney (rs = 0.718), liver (rs = 0.656), and brain (rs = 0.512) tissues (all p < 0.001). The median (25th percentile-75th percentile) concentration for placental T-Hg in the NTD case group was 8.91 (5.00-17.1) ng/g dry weight (d.w.), significantly higher than that in the healthy control group (4.99 [3.26-7.93] ng/g d.w., p < 0.001). After adjusting for potential confounders, higher levels of T-Hg in placenta were associated with increased risk for NTDs in offspring (OR = 1.76, 95% CI: 1.13-2.76), and a dose-response relationship was found (p < 0.001). CONCLUSION: The concentration of T-Hg in placenta is a good biomarker for estimating prenatal Hg exposure, which is associated with increased risk for NTDs.


Assuntos
Exposição Materna/efeitos adversos , Mercúrio , Compostos de Metilmercúrio , Defeitos do Tubo Neural , Biomarcadores , China/epidemiologia , Feminino , Humanos , Recém-Nascido , Mercúrio/análise , Mercúrio/toxicidade , Compostos de Metilmercúrio/toxicidade , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/epidemiologia , Gravidez
14.
Sci Total Environ ; 764: 144245, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33385660

RESUMO

Neural tube defects (NTDs) have a complex etiology. Few studies have assessed alkaline earth metals exposures and occurrence of NTDs. We examined the association between prenatal exposure to magnesium (Mg), calcium (Ca), strontium (Sr) and barium (Ba) and risk for NTDs in a case-control study, and assessed the teratogenic effects of Ba on mice. Placentas were collected from 408 women with NTD-affected pregnancies and 593 women who delivered healthy infants, and concentrations of these metals were determined as prenatal exposure markers. The single effect of individual exposure and joint effect of coexposure to these metals were evaluated with logistic regression and Bayesian kernel machine regression (BKMR), respectively. Barium chloride (BaCl2) was intragastrically administered to pregnant ICR mice and fetal mice were examined for NTDs. Median concentrations of Mg and Ba were higher in NTD cases than in controls (Pall < 0.001). In logistic regression, higher levels of Ba were associated with 1.6-fold increased risk for NTDs (95% confidence interval: 1.06-2.43). In BKMR, the joint effect of the four-metal mixture on NTD risk increased steadily with the levels of the mixture. A change in Ba concentration from the 25th to 75th percentile displayed a risk effect when the other three metals were fixed at the 25th, 50th or 75th percentile, while such a change in Ca concentration showed a protective effect when the other metals were held at the 25th or 50th percentile. No interactions among metals were found. In the mouse experiment, dams treated with 200 mg/kg BaCl2 showed 16.8% of NTDs in fetal mice, compared to 2.6% in the untreated control group (P < 0.01). Taken together, higher mixture levels of the four alkaline earth metals were associated with increased risk for NTDs, with Ba being the major contributor for the joint effect. Intragastric administration of Ba can induce NTDs in mice.


Assuntos
Defeitos do Tubo Neural , Efeitos Tardios da Exposição Pré-Natal , Animais , Bário/toxicidade , Teorema de Bayes , Estudos de Casos e Controles , Feminino , Camundongos , Camundongos Endogâmicos ICR , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/epidemiologia , Gravidez
15.
Br J Nutr ; 126(10): 1558-1563, 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33494841

RESUMO

Folic acid (FA) can reduce the risk for selected birth defects other than neural tube defects. We examined whether FA has preventive effects against fetal abdominal wall defects (AWD) in a unique intervention cohort in China. Birth outcomes of 247 831 singleton births from a population-based cohort study with detailed pre-conceptional FA intake information were collected in China in 1993-1996. Information on births at 20 complete gestational weeks, including live births, stillbirths and pregnancy terminations, and all structural birth defects regardless of gestational week were recorded. The birth prevalence of omphalocele, gastroschisis and total fetal AWD was classified by maternal FA supplementation. The prevalence of total AWD was 4·30 per 10 000 births among women who took FA compared with 13·46 per 10 000 births among those who did not take FA in northern China and 6·28 and 5·18 per 10 000 births, respectively, in southern China. The prevalence of omphalocele was 0·54 per 10 000 births among women who took FA compared with 3·74 per 10 000 births among those who did not take FA in northern China and 1·79 and 1·44 per 10 000 births, respectively, in southern China. FA supplementation significantly prevented total AWD in multivariate analysis (relative risk 0·26, 95 % CI 0·11, 0·61) in northern China, although no preventive effect of FA on AWD was observed in southern China. FA supplementation successfully reduced the prevalence of AWD in northern China.

16.
Epigenetics ; : 1-14, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33491544

RESUMO

Neural tube defects (NTDs) are a group of common and severe congenital malformations. The PI3K-AKT signalling pathway plays a crucial role in the neural tube development. There is limited evidence concerning any possible association between aberrant methylation in PI3K-AKT signalling pathway genes and NTDs. Therefore, we aimed to investigate potential associations between aberrant methylation of PI3K-AKT pathway genes and NTDs. Methylation studies of PI3K-AKT pathway genes utilizing microarray genome-methylation data derived from neural tissues of ten NTD cases and eight non-malformed controls were performed. Targeted DNA methylation analysis was subsequently performed in an independent cohort of 73 NTD cases and 32 controls to validate the methylation levels of identified genes. siRNAs were used to pull-down the target genes in human embryonic stem cells (hESCs) to examine the effects of the aberrant expression of target genes on neural cells. As a result, 321 differentially hypermethylated CpG sites in the promoter regions of 30 PI3K-AKT pathway genes were identified in the microarray data. In target methylation analysis, CHRM1, FGF19, and ITGA7 were confirmed to be significantly hypermethylated in NTD cases and were associated with increased risk for NTDs. The down-regulation of FGF19, CHRM1, and ITGA7 impaired the formation of rosette-like cell aggregates. The down-regulation of those three genes affected the expression of PAX6, SOX2 and MAP2, implying their influence on the differentiation of neural cells. This study for the first time reported that hypermethylation of PI3K-AKT pathway genes such as CHRM1, FGF19, and ITGA7 is associated with human NTDs.

17.
Sci Total Environ ; 770: 145284, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33515890

RESUMO

Neural tube defects (NTDs) are among the most common and disabling fetal congenital defects. Organochlorine pesticides (OCPs) are ubiquitous in the environment. In this study, 119 women who had NTD-affected pregnancies (cases) and 119 women who delivered healthy neonates (controls) were recruited in a rural area of Northern China. We used concentrations of OCPs in umbilical cord tissue as markers of prenatal exposure to investigate the association between in utero exposure to OCPs and NTD risk. Concentrations of 20 OCPs were quantified by gas chromatography-mass spectrometry, and 16 of the 20 OCPs were included in the analyses. Odds ratios and 95% confidence intervals (95% CIs) for the associations between levels of individual OCPs and NTD risk were estimated separately with logistic regression adjusting for potential confounders. The combined effects of exposure to the 16 OCPs as a mixture were analyzed with Bayesian kernel machine regression (BKMR). Logistic regression showed that the risk for NTDs increased 5.44-fold (95% CI, 2.21-13.41) for ß-hexachlorocyclohexane, 2.51-fold (95% CI, 1.07-5.86) for endosulfan I, 3.78-fold (95% CI, 1.60-8.89) for endosulfan II, 3.42-fold (95% CI, 1.44-8.12) for ο,ρ'-dichlorodiphenyldichloroethane, and 2.89-fold (95% CI, 1.22-6.86) for ρ,ρ'-dichlorodiphenyltrichloroethane when the concentration of each of these OCPs was above its median (exposed) compared to below its median (non-exposed). Other OCPs were not associated with NTD risk in multivariate models. In BKMR, NTD risk increased almost linearly with concentrations of the 16 OCPs as a mixture, which suggests joint effects on NTD risk. Exposure to α-hexachlorocyclohexane, ß-hexachlorocyclohexane, endosulfan II, ο,ρ'-dichlorodiphenyldichloroethane, and ρ,ρ'-dichlorodiphenyldichloroethane was associated with an increased risk for NTDs when levels of the remaining 15 OCPs were taken into account. Taken together, these findings show that prenatal exposure to OCPs is associated with increased risk for NTDs.


Assuntos
Hidrocarbonetos Clorados , Defeitos do Tubo Neural , Praguicidas , Efeitos Tardios da Exposição Pré-Natal , Teorema de Bayes , China/epidemiologia , Feminino , Humanos , Hidrocarbonetos Clorados/análise , Recém-Nascido , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/epidemiologia , Gravidez
18.
Ecotoxicol Environ Saf ; 208: 111632, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396152

RESUMO

Titanium (Ti) is commonly used in additives in the form of titanium dioxide (TiO2). However, our understanding of the effect of Ti on reproductive health remains limited. This nested case-control study, performed in a Ti mining exposure field, investigated the association between maternal blood Ti concentration and the risk of low birth weight (LBW), as well as the potential biological mechanism. A total of 45 women who delivered LBW infants (cases) and 352 women with normal birth weight infants (controls) were included. We collected maternal peripheral blood samples in the first or early second trimester to measure Ti concentration in serum (Tisr) and blood cells (Tibc), as well as inflammatory, lipid, and oxidative stress biomarkers thereof. The demographic characteristics of the women included in the study were also obtained. The results showed that the median total blood Ti concentration (Titb) in the case group was significantly higher than that in the control group (134 vs. 129 ng/mL, P = 0.039). A higher Titb level was associated with a greater risk of LBW [odds ratio = 2.62; 95% confidence interval (CI): 1.16-5.90], but no such association was observed for Tisr or Tibc after adjusting for potential confounders. The serum lipid biomarkers TC, TG, and total lipids (TL) were all negatively associated with Tisr and Titb. Serum 8-OHdG was positively associated with Tibc. We concluded that a high Titb during early pregnancy may increase the risk of LBW. Lipid metabolism and oxidative stress may play an important role in the adverse health effects associated with Ti exposure. Thus, our results merit more attention to the probable adverse effects of titanium exposure during pregnancy.


Assuntos
Recém-Nascido de Baixo Peso , Exposição Materna/efeitos adversos , Saúde Reprodutiva , Titânio/toxicidade , Adulto , Estudos de Casos e Controles , China , Feminino , Humanos , Recém-Nascido , Metabolismo dos Lipídeos/efeitos dos fármacos , Razão de Chances , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Titânio/sangue
19.
Public Health Nutr ; 24(13): 4238-4244, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33494847

RESUMO

OBJECTIVE: We examined whether folic acid (FA) supplementation prevented congenital hydrocephalus (CH) in more than 200 000 births in China. DESIGN: A large population-based cohort study. SETTING: All births at 20 complete gestational weeks, including live births, stillbirths and pregnancy terminations, and all structural birth defects regardless of gestational week were recorded. The prevalence of births with CH was classified by maternal characteristics and FA supplementation. CH was diagnosed in accordance with code 742.3 of the International Classification of Diseases, Ninth Revision, Clinical Modification, while non-neural tube defect (NTD) CH refers to CH without anencephaly (740), spina bifida (741) or encephalocele (742·0). PARTICIPANTS: A total of 247 831 pregnant women who delivered with known outcomes were included. RESULTS: A total of 206 cases of CH (0·83 per 1000 births) and 170 cases of non-NTD CH (0·69 per 1000 births) were recorded in the study. The prevalence of CH and non-NTD CH was higher in women in the no supplementation group than those in the FA supplementation group (0·92 and 0·72 v. 0·75 and 0·65 per 1000 births, respectively). FA supplementation during the periconceptional period significantly prevented CH (OR = 0·29, 95 % CI 0·12, 0·69) and non-NTD CH (OR = 0·34, 95 % CI 0·12, 0·97) in northern China, especially in a high-compliance group (≥ 80 %). CONCLUSIONS: Periconceptional FA supplementation did not significantly prevent CH overall in the current study. However, in the north of China with common maternal folate insufficiency, there was some evidence.

20.
J Matern Fetal Neonatal Med ; 34(11): 1754-1762, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31331218

RESUMO

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is one of the most serious birth complications for neonates. Few studies reported the relationship between maternal blood pressure disorders and risk of neonatal HIE. OBJECTIVE: This study was conducted to examine whether maternal hypertensive disorders in pregnancy increase the risk of HIE. METHODS: The analyses were performed using data from a large population-based cohort study aiming to prevent neural tube defects by supplementation with folic acid. The subjects comprised 183,981 women with singleton live births delivered at gestational ages of 32-42 weeks, who registered in two southern provinces in China. Blood pressure was measured by trained health care workers at each prenatal visit. Diagnosis information on HIE was recorded at the time of delivery. RESULTS: Totally 19,298 women (10.49%) were diagnosed with maternal hypertensive disorders in pregnancy and 255 infants (1.4 per 1000) with HIE, respectively. Compared with the normotensive group, a great increment in the risk of HIE was observed in women with hypertensive disorders (adjusted RR = 2.40, 95% confidence interval [CI]: 1.79-3.22) after adjusting for maternal confounding factors. A greater association was presented among preterm (32-36 weeks) infants with an adjusted RR of 5.45 (95% CI: 2.79, 10.65) compared to a RR of 2.09 (95% CI: 1.49, 2.92) among full-term (37-42 weeks) infants (p for heterogeneity < .05). Further stratification analyses showed that no matter with or without small for gestational age (SGA), maternal hypertensive disorders were associated with the increased risk for HIE. Sensitivity analyses excluding infants with low or high birth weight did not appreciably change the findings. CONCLUSIONS: Our present study demonstrated a positive association of maternal hypertensive disorders in pregnancy with the risk of neonatal HIE.


Assuntos
Hipertensão Induzida pela Gravidez , Hipóxia-Isquemia Encefálica , China , Estudos de Coortes , Feminino , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Hipóxia-Isquemia Encefálica/epidemiologia , Lactente , Recém-Nascido , Isquemia , Gravidez
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