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Objective

To examine the association of placental levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and chromium (Cr) with birth outcomes (birth weight, length, and head circumference, low birth weight [LBW], gestational age, preterm delivery, and small for gestational age [SGA]) in mother-child pairs from the Environment and Childhood (INMA) Project in Spain.

Methods

Metal concentrations were measured in placenta tissue samples randomly selected from five INMA cohorts. Data on birth outcomes were obtained from medical records. Associations were assessed in a sub-sample of 327 mother-infant pairs by regression models adjusted for confounding factors and for all metals simultaneously. Effect modification by sex was also evaluated.

Results

Elevated placental Cd levels (>5.79 vs. <3.30?ng/g) were associated with reduced birth weight (?111.8?g, 95%CI?=??215.6; ?8.06, p-trend?=?0.01) and length (?0.62?cm, 95%CI?=??1.20; ?0.04, p-trend?=?0.02), while a 10% increase in Cd was associated with 1.21-fold increased odds (95%CI?=?1.01; 1.43) of LBW in the global sample but with 14% lower odds (95%CI?=?0.78; 0.96) of preterm delivery in males (Pinteraction?=?0.10). Detected (vs. undetected) Hg was associated with reduced head circumference (?0.49?cm, 95%CI?=??1.00; 0.03) in females (Pinteraction?=?0.03). A 10% increase in placental Mn was associated with slight increases in gestational age (0.04 weeks, 95%CI?=?0.01; 0.07) in the global sample and in head circumference (0.05?cm, 95%CI?=??0.01; 0.10) in females (Pinteraction?=?0.03). Elevated Cr levels (>99.6 vs. <56.1?ng/g) were associated with reduced birth length (?0.68?cm, 95%CI?=??1.33; ?0.04, p-trend?=?0.02) and slightly increased gestational age (0.35 weeks, 95%CI?=??0.07; 0.77, p-trend?=?0.08) in the global sample. As and Pb were detected in few placentas (27% and 13%, respectively) and were not associated with any studied birth outcome.

Conclusions

Data suggest that in utero exposure to Cd, Hg, and Cr could adversely affect fetal growth, whereas Mn and Cr appear to have a positive effect on gestational age. Given the relatively small number of subjects, sex-specific associations should be interpreted with caution.  相似文献   
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Over 36 million people worldwide are infected with HIV. Antiretroviral therapy (ART) has proven to be highly effective to prevent HIV-1 transmission, clinical progression and death. Despite this success, the number of HIV-1 infected individuals continues increasing and ART should be taken for life. Therefore, there are two main priorities: the development of preventive vaccines to protect from HIV acquisition and achieve an efficient control of HIV infection in the absence of ART (functional cure). In this sense, in the last few years, there has been a broad interest in new and innovative approaches such as mRNA-based vaccines. RNA-based immunogens represent a promising alternative to conventional vaccines because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. Some mRNA-based vaccines platforms against infectious diseases have demonstrated encouraging results in animal models and humans. However, their application is still limited because the instability and inefficient in vivo delivery of mRNA. Immunogens, design, immunogenicity, chemical modifications on the molecule or the vaccine delivery methods are all crucial interventions for improvement. In this review we, will present the current knowledge and challenges in this research field. mRNA vaccines hold great promises as part of a combined strategy, for achieving HIV functional cure.  相似文献   
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