Placental metal concentrations and birth outcomes: The Environment and Childhood (INMA) project

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.

Mediterranean diet adherence during pregnancy and fetal growth: INMA (Spain) and RHEA (Greece) mother-child cohort studies

Dietary intake of specific nutrients or food groups during pregnancy could influence fetal growth, but scant evidence is available on effects of dietary patterns. The aim of this study was to evaluate the impact of Mediterranean diet (MD) adherence during pregnancy on fetal growth in two population-based mother-child cohorts in Spain and Greece. We studied 2461 mother-newborn pairs from the Spanish multi-centre 'INMA' study (Atlantic area: INMA-Atlantic; Mediterranean area: INMA-Mediterranean), and 889 pairs from the 'RHEA' study in Crete, Greece. Maternal diet during pregnancy was assessed by FFQ and MD adherence was evaluated through an a priori score. Fetal growth restriction was based on a customised model, and multivariate log-binomial and linear regression models were used to adjust for several confounders. MD scores differ significantly between the cohorts with women in INMA-Atlantic reporting higher intakes of fish and dairy products, while women in the Mediterranean area reported higher intakes of cereals, vegetables and fruits. Women with high MD adherence had a significantly lower risk of delivering a fetal growth-restricted infant for weight (risk ratios: 0·5; 95?% CI 0·3, 0·9) in the INMA-Mediterranean cohort. Stratified analysis by smoking revealed that higher MD adherence increased birth weight and birth length in smoking mothers, whereas this effect was not apparent in non-smoking mothers. The results of the present study show that several types of MD exist across European Mediterranean regions. High MD adherence may modify the detrimental effect of smoking on birth size, but overall effects of diet were not universal for the studies in this analysis.     

Redefining the “rational use of medicines”

For a long time, the definition of “Rational Use of Drugs” has set the basic conceptual framework for health providers worldwide to implement relevant recommendations about drug use, improving the quality of the lives of patients. However, we believe this definition needs an urgent update to incorporate One-Health's philosophy.     

A cluster randomized non-inferiority field trial on the immunogenicity and safety of tetanus toxoid vaccine kept in controlled temperature chain compared to cold chain

Background

In resource-poor settings, cold chain requirements present barriers for vaccine delivery. We evaluated the immunogenicity and safety of tetanus toxoid (TT) vaccine in “Controlled Temperature Chain” (CTC; up to 40 °C for <30 days before administration), compared to standard cold chain (SCC; 2–8 °C). Prior to the study, stability parameters of TT–CTC were shown to meet international requirements.

Methods

A cluster randomized, non-inferiority trial was conducted in Moïssala district, Chad, December 2012–March 2013. Thirty-four included clusters were randomized to CTC or SCC. Women aged 14–49 years, eligible for TT vaccination and with a history of ≤1 TT dose, received two TT doses 4 weeks apart. Participants were blinded to allocation strategy. Tetanus antibody titers were measured using standard ELISA at inclusion and 4 weeks post-TT2. Primary outcome measures were post-vaccination seroconversion and fold-increase in geometric mean concentrations (GMC). Non-inferiority was by seroconversion difference (TT_SCC − TT_CTC) <5% and ratio of GMCs (TT_SCC/TT_CTC) <1.5. Adverse events were monitored at health centers and at next contact with participants.

Results

A total of 2128 women (CTC = 1068; SCC = 1060) were recruited. Primary intention to vaccinate analysis included 1830 participants; 272 of these were included in the seroconversion analysis. Seroconversion was reached by >95% of participants; upper 95%CI of the difference was 5.6%. Increases in GMC were over 4-fold; upper 95%CI of GMC ratio was 1.36 in the adjusted analysis. Few adverse events were recorded.

Conclusions

This study demonstrates the immunogenicity and safety of TT in CTC at <40 °C for <30 days. The high proportion of participants protected at baseline results in a reduction of power to detect a 5% non-inferiority margin. However, results at a 10% non-inferiority margin, the comparable GMC increases and vaccine's stability demonstrated in the preliminary phase indicate that CTC can be an alternative strategy for TT delivery in situations where cold chain cannot be maintained.     

Regulation of the inflammatory response by tin protoporphyrin IX in the rat anterior cruciate ligament transection model of osteoarthritis

The purpose of this study was to investigate several inflammatory mediators and cartilage degradation molecules as possible biomarkers of joint lesion in the anterior cruciate ligament transection (ACLT) model of osteoarthritis in rats. We also assessed whether the treatment with the anti‐inflammatory agent tin protoporphyrin IX (SnPP) reduces the progression of disease. Our results indicate that serum levels of interleukin (IL)‐6 and PGE₂ are significantly increased in ACLT rats 10 weeks after surgery, whereas the increases in IL‐1β and tumor necrosis‐α were not significant. In addition, our data suggest that IL‐17 is the main pro‐inflammatory cytokine in the ACLT joint. We have shown that serum C‐telopeptide of type II collagen (CTX‐II) is a biomarker better than cartilage oligomeric matrix protein, whereas hyaluronic acid showed no correlation with disease progression. Administration of SnPP (i.p. 12 mg/kg BW/day for 10 weeks) reduces the severity of structural changes and the levels of CTX‐II, IL‐6, and PGE₂ in serum and IL‐17 and PGE₂ in ACLT knees. These effects on PGE₂ are dependent on the down‐regulation of cyclooxygenase‐2. Our findings indicate that systemic and local inflammatory mediators participate in the rat ACLT model and anti‐inflammatory strategies may help to reduce the progression of joint lesion. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1375–1382, 2011     

Analysis of early biochemical markers and regulation by tin protoporphyrin IX in a model of spontaneous osteoarthritis

Age-related changes in joint tissues lead to osteoarthritis (OA). Detection of early changes in OA patients may help to initiate treatments before the establishment of irreversible joint destruction. STR/ort mice develop with age a severe degenerative joint disease that resembles human OA thus allowing the investigation of biochemical markers as well as new treatments in an accelerated time frame. We have analyzed the changes in serum levels of different mediators during the early phases of idiopathic OA in STR/ort mice. Serum levels of matrix metalloproteinase-3 (MMP-3) but not those of tumor necrosis factor-α, interleukin(IL)-1β, IL-17 or prostaglandin E(2) correlated with histopathological changes in knees of STR/ort mice at 9 weeks. Treatment of animals with tin protoporphyrin IX (SnPP, 12 mg/kg/dayi.p.) for 4 weeks significantly reduced the progression of OA. Our data suggest that MMP-3 is a sensitive biomarker to detect early OA alterations and that SnPP could be a protective agent in OA.     

Exposure to second-hand smoke and reproductive outcomes depending on maternal asthma

Tobacco consumption and exposure to second-hand smoke (SHS) are associated with reduced birth weight. One issue that has not been clarified previously is that of the potential higher risk of this outcome in mothers with asthma. We assessed the role of prenatal maternal tobacco use and SHS on reproductive outcomes and assessed the interaction with maternal history of asthma. Data was collected from the INMA study, a maternal birth cohort selected from the general population established in Spain in 2002. We measured cotinine at the 32nd week of pregnancy in 2,219 females. Diagnosed maternal asthma was self-reported during pregnancy. 35% of mothers reported not being exposed to smoking or SHS during pregnancy. Active smoking (i.e. self-reported or cotinine >50 ng·mL(-1)) was related to a 134 g decrease in birth weight and a relative risk of 1.8 for small for gestational age and fetal growth restriction. These results were not modified by maternal asthma. Maternal asthma had a similar frequency in all exposure groups. Non SHS-exposed females had the lowest prevalence of asthma. SHS (i.e. cotinine 20-50 ng·mL(-1)) decreased birth weight by 32 g among those without maternal asthma, but these differences were not statistically significant (95% CI -88.76-24.76). Maternal asthma did not promote these effects. Maternal history of asthma did not modify the effects of smoking on reproductive outcomes in a cohort sampled from the general population.