Interaction effects of MTHFR C677T and A1298C polymorphisms with maternal glycated haemoglobin levels on adverse birth outcomes.

AIMS: The role of maternal genetic factors in the association between high glycated haemoglobin (HbA1c) levels and adverse birth outcomes remains unclear. MATERIALS AND METHODS: In this study, the maternal HbA1c levels of 5108 normoglycemic pregnant women in China were measured, and A1298C and C677T polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene were genotyped. RESULTS: Elevated HbA1c levels during the second trimester were associated with increased risks of macrosomia, large-for-gestational age (LGA), preterm birth (PTB), and reduced gestational age (p < 0.05). Pregnant women with MTHFR A1298C AA or C677T CT + TT genotypes were susceptible to adverse pregnancy outcomes related to HbA1c levels. Among pregnant women with the A1298C AA genotype, each standard deviation (SD) increase in HbA1c levels increased the risk of PTB by 1.32-times and reduced the gestational age by 0.11 weeks (p < 0.05). For MTHFR C677T CC + TT genotype carriers, higher HbA1c levels were associated with 1.49-, 1.24-, and 1.23-times increased risks of macrosomia, LGA, and PTB, respectively (p < 0.05). A U-shaped curve for PTB risk in relation to HbA1c levels was observed among the C677T CC + TT participants, with a cut-off value of 4.58%. Among subjects with the A1298C AA genotype combined with the C677T CT + TT genotype, each SD increase in HbA1c levels was associated with 1.40 and 1.37-times increased risks of LGA and PTB, respectively. CONCLUSIONS: Our findings highlight the importance of glycaemic control during pregnancy and the potential impact of genetic factors on birth outcomes. However, further large-scale studies are required to confirm these findings.

Blood-cerebrospinal fluid barrier permeability of metals/metalloids and its determinants in pediatric patients.

Concerns regarding adverse effects of metal/metalloids exposure on brain development and neurological disorders among children are increasing. However, the transport patterns of metals/metalloids across the blood-cerebrospinal fluid barrier (BCSFB) need to be clarified in children. A total of 99 Chinese pediatric patients were enrolled from February 2020 to August 2021, with a median age of 6.76 months. We detected 16 metal/metalloid levels in matched serum and cerebrospinal fluid (CSF) samples using inductively coupled plasma mass spectrometry. The BCSFB permeability of metals/metalloids were estimated and the potential effects of biomedical parameters were explored. Most metals/metalloids were detectable among > 80.0% of CSF samples. Significant correlations were observed between strontium (Sr, r = 0.46), molybdenum (Mo, r = 0.50), and cadmium (Cd, r = 0.24) concentrations in serum and CSF (P < 0.05). Ratios of metal/metalloid levels in CSF to serum (Rmetal) ranged from 0.02 to 0.74, and hazardous metals/metalloids including arsenic (As), Cd, lead (Pb), thallium (Tl), and manganese (Mn) showed high transfer efficiencies across the BCSFB (Rmetals > 0.5). With the adjustment of age and sex, albumin, ß2-microglobulin, and total protein levels in CSF were positively associated with copper (Cu) permeability (FDR-adjusted P < 0.05), while glucose in CSF was negatively correlated with calcium (Ca), Cu, Sr, and Mo BCSFB permeability (FDR-adjusted P < 0.05). Q-Alb promoted Cu permeability across the BCSFB (FDR-adjusted P < 0.001), while C-reactive protein levels in serum were positively associated with selenium (Se) permeability (FDR-adjusted P = 0.046). For the first time, our findings provided data for the BCSFB permeability of 16 metals/metalloids in children, and indicated that some biomedical parameters could influence the transformation of metals/metalloids from serum to CSF. Metals/metalloids with strong BCSFB permeability warrant attention for their potential neurotoxicity.

Association between phthalate exposure and asthma risk: A meta-analysis of observational studies.

BACKGROUND: Phthalates are ubiquitously found in numerous environments and have been related to a variety of adverse health effects. Previous studies have suggested that phthalate exposure is associated with asthma risk in humans; however, such findings are inconsistent. METHODS: The aim of the present meta-analysis was to clarify the association between phthalate exposure and asthma risk. A literature search was conducted using PubMed, EMBASE and Web of Science for relevant studies published up to January 5, 2020. Fixed-effects or random-effects models were applied to combine the results, and several subgroup analyses were used to explore the sources of heterogeneity. RESULTS: A total of 14 studies containing more than 14,000 participants were included in the present study. A positive, significant association between mono-benzyl phthalate (MBzP) levels and asthma risk was found, and the overall odds ratio (OR) was 1.17 (95% confidence interval [CI]: 1.06-1.28, P-value for overall effect [Pz] = 0.001), with a low heterogeneity (P-value for heterogeneity [Phet] = 0.193, I2 = 23.6%). The pooled ORs for mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) concentrations were 1.13 (95% CI: 1.03-1.24, Pz = 0.011) and 1.20 (95% CI: 1.00-1.42, Pz = 0.045), respectively. Children with high levels of MBzP or mono-(carboxynonyl) phthalate (MCNP) were suggested to have increased odds of asthma compared to older populations. In the subgroup analysis by study location, an increased risk for asthma in relation to levels of the sum of di-2-ethylhexyl phthalate (ΣDEHP) was observed in European studies (OR = 1.16, 95% CI: 1.00-1.34, Pz = 0.048) compared to Asia and North America. CONCLUSIONS: Urinary levels of MBzP, MEHHP, MECPP, MCNP, and DEHP were positively related to asthma risk. No significant association was observed for the other phthalate metabolites in relation to asthma risk. Further research is needed to verify these findings and shed light on the molecular mechanism by which phthalates are associated with asthma.