Use of multiple sclerosis disease-modifying therapies during pregnancy in France: Nationwide study between 2010 and 2021.

BACKGROUND: Multiple sclerosis (MS) frequently affects women of childbearing age and pregnant women. OBJECTIVE: To assess the use of MS disease-modifying therapies (DMTs) during pregnancy in France over the last decade, marked by an increasing DMTs availability. METHODS: All pregnancies ended from April 2010 to December 2021 in women with MS were identified based on the nationwide Mother-Child Register EPI-MERES, built from the French National Health Data System (Système National des Données de Santé (SNDS)). RESULTS: Of a total of 20,567 pregnancies in women with MS, 7587 were exposed to DMT. The number of DMT-exposed pregnancies markedly increased from 1079 in 2010-2012 to 2413 in 2019-2021 (+124%), especially those exposed to glatiramer acetate, natalizumab, dimethyl fumarate, and anti-CD20. Among pregnancies of women on DMT 6 months before pregnancy, 78.0% underwent DMT discontinuation and 7.6% switched DMT, generally before (33.0% and 77.0%, respectively) or during the first trimester of pregnancy (58.3% and 17.8%, respectively). DMT discontinuation decreased from 84.0% in 2010-2012 to 72.4% in 2019-2021 and was less frequent among women aged ⩾35 years and those socioeconomically disadvantaged. CONCLUSION: Despite MS therapeutic management adaptations to pregnancy, exposure during pregnancy to treatments whose safety profile has not yet been clearly established has increased sharply over the last decade.

A multidisciplinary and structured investigation of three suspected clusters of transverse upper limb reduction defects in France.

INTRODUCTION: Between 2019-2021, facing public concern, a scientific expert committee (SEC) reanalysed suspected clusters of transverse upper limb reduction defects (TULRD) in three administrative areas in France, where initial investigations had not identified any risk exposure. We share here the national approach we developed for managing suspicious clusters of the same group of congenital anomalies occurring in several areas. METHODS: The SEC analysed the medical records of TURLD suspected cases and performed spatiotemporal analyses on confirmed cases. If the cluster was statistically significant and included at least three cases, the SEC reviewed exposures obtained from questionnaires, environmental databases, and a survey among farmers living near to cases' homes concerning their plant product use. RESULTS: After case re-ascertainment, no statistically significant cluster was observed in the first administrative areas. In the second area, a cluster of four children born in two nearby towns over two years was confirmed, but as with the initial investigations, no exposure to a known risk factor explaining the number of cases in excess was identified. In the third area, a cluster including just two cases born the same year in the same town was confirmed. DISCUSSION: Our experience highlights that in the event of suspicious clusters occurring in different areas of a country, a coordinated and standardised approach should be preferred.

Body composition and anthropometric indicators as predictors of blood pressure: a cross-sectional study conducted in young Algerian adults.

Various body indicators are used to predict health risks. However, controversies still exist regarding the best indicators to predict CVD. Using a large number of measurements, our aim was to assess their associations with blood pressure (BP) and to identify the most relevant parameters to be used in health surveillance studies. The population included 589 students (67·2 % women) aged 20-25 years from Constantine (Algeria). Sixteen parameters were considered, including crude body measurements, ratios and body fat indicators based on bioelectrical impedance analysis (BIA). We used multi-adjusted linear regression models to assess the associations between body measurements and BP. According to WHO definitions, underweight, overweight-without obesity, obesity and hypertension (HT) were identified in 6·1, 18·0, 2·4 and 5·1 % of the subjects, respectively. Prevalence of HT was higher in men than in women (11·9 % v. 1·8 %; P < 0·001). In the whole sample, almost all indicators were positively associated with systolic and diastolic BP. The suprailiac skinfold had the strongest associations with systolic (ß = 3·498; P < 0·001) and diastolic (ß = 2·436; P < 0·001) BP, and as a whole, arm circumferences and weight were also good candidates. The currently used BMI, waist-to-hip, waist-to-height ratio and BIA indictors also predicted BP, but they did not seem to be better determinants of BP than crude anthropometric measurements. This study showed that overweight and HT were already found in the present population of young Algerian adults. Most body indicators were highly associated with BP, but simple anthropometric measurements appeared to be particularly useful to predict BP.

Risk for Myocardial Infarction, Stroke, and Pulmonary Embolism Following COVID-19 Vaccines in Adults Younger Than 75 Years in France.

BACKGROUND: The BNT162b2 (Pfizer-BioNTech) vaccine has been shown to be safe with regard to risk for severe cardiovascular events (such as myocardial infarction [MI], pulmonary embolism [PE], and stroke) in persons aged 75 years or older. Less is known about the safety of other COVID-19 vaccines or outcomes in younger populations. OBJECTIVE: To assess short-term risk for severe cardiovascular events (excluding myocarditis and pericarditis) after COVID-19 vaccination in France's 46.5 million adults younger than 75 years. DESIGN: Self-controlled case series method adapted to event-dependent exposure and high event-related mortality. SETTING: France, 27 December 2020 to 20 July 2021. PATIENTS: All adults younger than 75 years hospitalized for PE, acute MI, hemorrhagic stroke, or ischemic stroke (n = 73 325 total events). MEASUREMENTS: Linkage between the French National Health Data System and COVID-19 vaccine databases enabled identification of hospitalizations for cardiovascular events (MI, PE, or stroke) and receipt of a first or second dose of the Pfizer-BioNTech, mRNA-1273 (Moderna), Ad26.COV2.S (Janssen), or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine. The relative incidence (RI) of each cardiovascular event was estimated in the 3 weeks after vaccination compared with other periods, with adjustment for temporality (7-day periods). RESULTS: No association was found between the Pfizer-BioNTech or Moderna vaccine and severe cardiovascular events. The first dose of the Oxford-AstraZeneca vaccine was associated with acute MI and PE in the second week after vaccination (RI, 1.29 [95% CI, 1.11 to 1.51] and 1.41 [CI, 1.13 to 1.75], respectively). An association with MI in the second week after a single dose of the Janssen vaccine could not be ruled out (RI, 1.75 [CI, 1.16 to 2.62]). LIMITATIONS: It was not possible to ascertain the relative timing of injection and cardiovascular events on the day of vaccination. Outpatient deaths related to cardiovascular events were not included. CONCLUSION: In persons aged 18 to 74 years, adenoviral-based vaccines may be associated with increased incidence of MI and PE. No association between mRNA-based vaccines and the cardiovascular events studied was observed. PRIMARY FUNDING SOURCE: None.

A modified self-controlled case series method for event-dependent exposures and high event-related mortality, with application to COVID-19 vaccine safety.

We propose a modified self-controlled case series (SCCS) method to handle both event-dependent exposures and high event-related mortality. This development is motivated by an epidemiological study undertaken in France to quantify potential risks of cardiovascular events associated with COVID-19 vaccines. Event-dependence of vaccinations, and high event-related mortality, are likely to arise in other SCCS studies of COVID-19 vaccine safety. Using this case study and simulations to broaden its scope, we explore these features and the biases they may generate, implement the modified SCCS model, illustrate some of the properties of this model, and develop a new test for presence of a dose effect. The model we propose has wider application, notably when the event of interest is death.

Burden and risk factors for relapse following successful treatment of uncomplicated severe acute malnutrition in young children: Secondary analysis from a randomised trial in Niger.

This study aimed to quantify the burden of relapse following successful treatment for uncomplicated severe acute malnutrition (SAM) and to identify associated risk factors in rural Niger. We used data from 1490 children aged 6-59 months discharged as recovered from an outpatient nutritional programme for SAM and followed for up to 12 weeks after admission. Postdischarge SAM relapse was defined as weight-for-height Z-score <-3, mid-upper arm circumference (MUAC) <115 mm or bipedal oedema after having been discharged as recovered. Postdischarge hospitalisation was defined as admission to inpatient SAM treatment or hospitalisation for any cause after having been discharged as recovered. We used multivariate log-binomial models to identify independent risk factors. After programmatic discharge, 114 (8%) children relapsed to SAM and 89 (6%) were hospitalised. Factors associated with SAM relapse were discharge during the lean season (relative risk [RR] = 1.80 [95% confidence interval [CI] = 1.22-2.67]) and larger household size (RR = 1.56 [95% CI = 1.01-2.41]), whereas older child age (RR = 0.94 [95% CI = 0.88-1.00]), higher child MUAC at discharge (RR = 0.93 [95% CI = 0.87-1.00]) and maternal literacy (RR = 0.54 [95% CI = 0.29-0.98]) were protective factors. Discharge during the lean season (RR = 2.27 [95% CI = 1.46-3.51]) was independently associated with postdischarge hospitalisation. Future nutritional programmes in the context of Niger may consider modification of anthropometric discharge criteria or the provision of additional home support or follow-up during the lean season as potential interventions to prevent relapse. More research including postdischarge follow-up is needed to better understand the sustainability of treatment outcomes after discharge and the type of intervention that may best sustain recovery over time. Clinical Trial Registration: ClinicalTrials.gov number, NCT01613547.

Early postnatal growth and subsequent neurodevelopment in children delivered at term: The ELFE cohort study.

BACKGROUND: Despite the limited evidence, accelerated early postnatal growth (EPG) is commonly believed to benefit neurodevelopment for term-born infants, especially those small for gestational age. OBJECTIVES: To investigate the existence of critical time windows in the association of EPG with neurodevelopment, considering birth size groups. STUDY DESIGN: In the French ELFE birth cohort, 12,854 term-born neonates were classified as small, appropriate or large for gestational age (SGA, AGA, LGA, respectively). Parents reported their child's development by using the Child Development Inventory (CDI-score) at age 12 months and the MacArthur-Bates Development Inventory (MAB-score; 100 score units) assessing language ability at age 24 months. Predictions of individual weight, body mass index (BMI), length, and head circumference (HC) from birth to age 24 months were obtained from repeated measurements fitted with the Jenss-Bayley mixed-effects model. For each infant, conditional gains (CG) in these growth parameters were generated at four-time points (3, 6, 12 and 24 months) representing specific variations in growth parameters during 0-3, 3-6, 6-12, 12-24 months, independent of previous measures. Using multivariable linear regression models, we provided the estimate differences of the neurodevelopmental scores according to variation of each growth parameter CG, by birth size group. RESULTS: For SGA infants, the MAB-score differed by 5.8 (95% confidence interval [CI] -0.2, 11.8), 6.7 (95% CI -0.1, 13.3), and 9.7 (95% CI 1.9, 17.5) score units when CG in BMI, weight, and HC at 3 months varied from -2 to 1 standard deviation, respectively. For all infants, MAB-score was linearly and positively associated with length conditional gains at 12 months, with stronger magnitude for SGA infants. Results for the CDI-score were overall consistent with those for MAB-score. CONCLUSIONS: For term-born SGA infants, moderate catch-up in HC, BMI and weight within the first 3 months of life may benefit later neurodevelopment, which could guide clinicians to monitor EPG.

Are selection criteria for healthy pregnancies responsible for the gap between fetal growth in the French national Elfe birth cohort and the Intergrowth-21st fetal growth standards?

BACKGROUND: The Intergrowth-21st (IG) project proposed prescriptive fetal growth standards for global use based on ultrasound measurements from a multicounty study of low-risk pregnancies selected using strict criteria. We examined whether the IG standards are appropriate for fetal growth monitoring in France and whether potential differences could be due to IG criteria for "healthy" pregnancies. METHOD: We analysed data on femur length and abdominal circumference at the second and/or the third recommended ultrasound examination from 14 607 singleton pregnancies from the Elfe national birth cohort. We compared concordance of centile thresholds using the IG standards and current French references and used restricted cubic splines to plot z-scores by gestational age. A "healthy pregnancy" sub-sample was created based on maternal and pregnancy selection criteria, as specified by IG. RESULTS: Mean gestational age-specific z-scores for femur length and abdominal circumference using French references fluctuated around 0 (-0.2 to 0.1), while those based on IG standards were higher (0.3-0.8). Using IG standards, 2.5% and 5.2% of fetuses at the third ultrasound were <10th centile for femur length and abdominal circumference, respectively, and 31.5% and 16.7% were >90th. Only 34% of pregnancies fulfilled IG low-risk criteria, but sub-analyses yielded very similar results. CONCLUSION: Intergrowth standards differed from fetal biometric measures in France, including among low-risk pregnancies selected to replicate IG's healthy pregnancy sample. These results challenge the project's assumption that careful constitution of a low-risk population makes it possible to describe normative fetal growth across populations.

Which modifiable prenatal factors mediate the relation between socio-economic position and a child's weight and length at birth?

Although several studies have shown a positive association between socio-economic position and size at birth, not enough is known about the modifiable factors that may be involved. We aimed to investigate whether maternal prepregnancy body mass index (BMI), smoking, diet, and depression during pregnancy mediate the positive association between maternal education and birth size. Weight and length z-scores specific for gestational age and sex were calculated for 1,500 children from the EDEN mother-child cohort. A mediation analysis of the associations between maternal education and birth size was conducted with a counterfactual method, adjusted for recruitment centre, parity, maternal height, and age. In the comparison of children of mothers with low versus intermediate education levels, maternal smoking during pregnancy explained 52% of the total effect of education on birth weight. Similar findings were observed with birth length z-score (37%). The comparison of children of mothers with high versus intermediate education levels yielded a non-significant total effect, which masked opposite mediating effects by maternal BMI and smoking during pregnancy on both birth weight and length. Prepregnancy BMI and maternal smoking during pregnancy mediate the positive association between maternal education and birth weight and length z-scores. These mediators, however, act in opposite directions, thereby masking the extent to which healthy prenatal growth is socially differentiated.

Early postnatal growth and neurodevelopment in children born moderately preterm or small for gestational age at term: A systematic review.

BACKGROUND: Clinicians' interest in the long-term effects of early postnatal growth (EPG) is growing. There is compelling evidence linking rapid EPG with later cardiovascular risk, but its neurodevelopmental benefits still remain hypothetical in individuals born moderately preterm (MP) or small for gestational at term (SGAT). METHODS: The objective was to perform a systematic review of the relationship between EPG before age 3 years and neurodevelopmental outcome for individuals born MP (32-36 weeks' gestational age) or SGAT. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, 3 independent investigators searched for articles published on this topic in the Web of Science, EMBASE and PubMed from database inception to July 1, 2017. A detailed quality scale was used to evaluate articles. RESULTS: We selected 19 articles relying on 12 distinct study populations; 7 articles from 3 study populations were considered at moderate or high quality. The lack of standardisation of growth analysis methods prevented performing a meta-analysis. Overall, EPG was positively associated with neurodevelopmental outcome, especially Intelligence Quotient (IQ) when available. In this relationship, the first 6 months of life might be a critical period. Analysis of the few articles investigating the shape of the relationships revealed a non-linear association, with a plateau for IQ with higher weight gain, which suggests a possible ceiling effect. CONCLUSIONS: A positive association was generally found between EPG and neurodevelopmental outcome for individuals born MP or SGAT. Strategies for future epidemiological studies are suggested to improve the characterisation of this relationship.

Prenatal exposure to glycol ethers and cryptorchidism and hypospadias: a nested case-control study.

OBJECTIVES: Glycol ethers (GE) are oxygenated solvents frequently found in occupational and consumer products. Some of them are well-known testicular and developmental animal toxicants. This study aims to evaluate the risk of male genital anomalies in association with prenatal exposure to GE using urinary biomarkers of exposure. METHODS: We conducted a case-control study nested in two joint mother-child cohorts (5303 pregnant women). Cases of cryptorchidism and hypospadias were identified at birth and confirmed during a 2-year follow-up period (n=14 cryptorchidism and n=15 hypospadias). Each case was matched to three randomly selected controls within the cohorts for region of inclusion and gestational age at urine sampling. Concentrations of five GE acidic metabolites were measured in spot maternal urine samples collected during pregnancy. ORs were estimated with multivariate conditional logistic regressions including a Firth's penalisation. RESULTS: Detection rates of urinary GE metabolites ranged from 8% to 93% and only two were sufficiently detected (>33%) in each cohort to be studied: methoxyacetic acid (MAA) and phenoxyacetic acid (PhAA). A significantly higher risk of hypospadias was associated with the highest tertile of exposure to MAA: OR (95% CI) 4.5(1.4 to 23.4). No association were observed with urinary concentration of PhAA, nor with the risk of cryptorchidism. CONCLUSIONS: In view of the toxicological plausibility of our results, this study, despite its small sample size, raises concern about the potential developmental toxicity of MAA on the male genital system and calls for thorough identification of current sources of exposure to MAA.

Dendritic cells' death induced by contact sensitizers is controlled by Nrf2 and depends on glutathione levels.

Dendritic cells (DC) are known to play a major role during contact allergy induced by contact sensitizers (CS). Our previous studies showed that Nrf2 was induced in DC and controlled allergic skin inflammation in mice in response to chemicals. In this work, we raised the question of the role of Nrf2 in response to a stress provoked by chemical sensitizers in DC. We used two well-described chemical sensitizers, dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA), known to have different chemical reactivity and mechanism of action. First, we performed a RT-qPCR array showing that CinA was a higher inducer of immune and detoxification genes compared to DNCB. Interestingly, in the absence of Nrf2, gene expression was dramatically affected in response to DNCB but was slightly affected in response to CinA. These observations prompted us to study DC's cell death in response to both chemicals. DNCB and CinA increased apoptotic cells and decreased living cells in the absence of Nrf2. The characterization of DC apoptosis induced by both CS involved the mitochondrial-dependent caspase pathway and was regulated via Nrf2 in response to both chemicals. Oxidative stress induced by DNCB, and leading to cell death, was regulated by Nrf2. Unlike CinA, DNCB treatment provoked a significant reduction of intracellular GSH levels and up-regulated bcl-2 gene expression, under the control of Nrf2. This work underlies that chemical reactivity may control Nrf2-dependent gene expression leading to different cytoprotective mechanisms in DC.

Joint Bayesian weight and height postnatal growth model to study the effects of maternal smoking during pregnancy.

Growth models used for describing the dynamics of body weight and height generally consider each trait independently. We proposed modeling height and weight trajectories jointly with a nonlinear heteroscedastic mixed model based on the Jenss-Bayley growth function with correlated individual random effects and using Bayesian inference techniques. Simulations showed that our model provides good estimates of the growth parameters. We illustrated how it can be used to assess the associations between maternal smoking during pregnancy, an early-life factor potentially involved in prenatal programming of obesity, and children's growth from birth to 5 years of age. We used real data from the EDEN study, a large French mother-child cohort study with a high number of height and weight measurements (a total of approximately 30 000 measurements for each of the 2 traits across the 1666 children). Our results supported the existence of a relationship between maternal smoking during pregnancy and growth from birth to 5 years of age. Children from mothers who smoked throughout pregnancy were shown to display a higher body mass index from the first few months of life onwards compared to children from nonsmokers. At 5 years of age, their mean body mass index was 0.21 kg/m2 higher than unexposed children. It was mainly explained by the fact that these children tended to be smaller at birth but rapidly exceeded the weight of children from nonsmokers postnatally.

Phthalate pregnancy exposure and male offspring growth from the intra-uterine period to five years of age.

OBJECTIVE: To study associations between prenatal exposure to phthalates and fetal and postnatal growth up to age 5 years in male offspring. METHODS: Eleven phthalate metabolites were quantified in spot maternal urine samples collected during gestation among 520 women of the EDEN mother-child cohort who gave birth to a boy. Fetal growth was assessed from repeated ultrasound measurements and measurements at birth. We used repeated measures of weight and height in the first 5 years of life to model individual postnatal growth trajectories. We estimated adjusted variations in pre and postnatal growth parameters associated with an interquartile range increase in ln-transformed phthalate metabolite concentrations. RESULTS: Monocarboxyisononyl phthalate (MCNP) was positively associated with femoral length during gestation and length at birth. High molecular weight phthalate metabolites were negatively associated with estimated fetal weight throughout pregnancy. Monoethyl phthalate (MEP) showed positive association with weight growth velocity from two to five years and with body mass index at five years (ß=0.17kg/m2, 95% confidence interval, 0.04, 0.30). CONCLUSIONS: We highlighted associations between gestational exposure to some phthalates and growth in boys. The positive association between MEP and postnatal growth in boys was also reported in several previous human studies.

Multidimensionality of the relationship between social status and dietary patterns in early childhood: longitudinal results from the French EDEN mother-child cohort.

BACKGROUND: The association between socioeconomic position and diet in early childhood has mainly been addressed based on maternal education and household income. We aimed to assess the influence of a variety of social factors from different socio-ecological levels (parents, household and child-care) on multi-time point dietary patterns identified from 2 to 5 y. METHOD: This study included 974 children from the French EDEN mother-child cohort. Two multi-time point dietary patterns were derived in a previous study: they correspond to consistent exposures to either core- or non-core foods across 2, 3 and 5 y and were labelled "Guidelines" and "Processed, fast-foods". The associations of various social factors collected during pregnancy (age, education level) or at 2-y follow-up (mother's single status, occupation, work commitments, household financial disadvantage, presence of older siblings and child-care arrangements) with each of the two dietary patterns, were assessed by multivariable linear regression analysis. RESULTS: The adherence to a diet close to "Guidelines" was positively and independently associated with both maternal and paternal education levels. The adherence to a diet consistently composed of processed and fast-foods was essentially linked with maternal variables (younger age and lower education level), household financial disadvantage, the presence of older sibling (s) and being cared for at home by someone other than the mother. CONCLUSIONS: Multiple social factors operating at different levels (parents, household, and child-care) were found to be associated with the diet of young children. Different independent predictors were found for each of the two longitudinal dietary patterns, suggesting distinct pathways of influence. Our findings further suggest that interventions promoting healthier dietary choices for young children should involve both parents and take into account not only household financial disadvantage but also maternal age, family size and options for child-care.

Postnatal weight growth and trihalomethane exposure during pregnancy.

BACKGROUND: Impaired postnatal growth after chloroform exposure in utero has been observed in rodents without an effect on birth weight. We aimed to study the relationship between exposure to trihalomethanes (THMs) during pregnancy and postnatal weight growth during infancy. METHODS: We analysed 2216 mother-child pairs recruited in Gipuzkoa, Sabadell, Valencia (Spain, INMA Project, enrollment: 2003-2008) and Crete (Greece, RHEA Study, enrollment: 2007-2008). Drinking water habits and water-related activities ascertained through personal interviews were combined with THM measurements in drinking water to estimate THM exposure through different exposure routes during pregnancy. Weight measurements during the first year of life were used to fit postnatal weight growth curves from birth to one year and to predict weight at six months. Multiple linear regression was used to evaluate the relationship between six months weight gain and interquartile range (IQR) increase in THM exposure adjusting for confounders. RESULTS: Average weight gain at six months ranged from 4325 g (Gipuzkoa) to 4668 g (Crete). Median residential THM levels ranged from 1 µg/l (Crete) to 117 µg/l (Sabadell). No significant association was observed overall (-24.4 g [95% CI -78.8, 30.0] for an IQR increase in total residential uptake). A negative relationship was observed in Sabadell (-148 g [95% CI -282, -13.7]) for an IQR increase in ingestion THM uptake. CONCLUSIONS: No consistent evidence of an association between THM exposure during pregnancy and postnatal growth was observed. The novelty of the hypothesis and the negative trend observed in the region with the highest levels warrants the replication in future studies.

Bisphenol A and the risk of cardiometabolic disorders: a systematic review with meta-analysis of the epidemiological evidence.

Bisphenol A (BPA) is suspected to be associated with several chronic metabolic diseases. The aim of the present study was to review the epidemiological literature on the relation between BPA exposure and the risk of cardiometabolic disorders. PubMed and Embase databases were searched up to August 2014 by two independent investigators using standardized subject terms. We included observational studies (cohort, case-control and cross-sectional studies) carried out in children or adults, measuring urinary BPA (uBPA), including at least 100 participants and published in English. The health outcomes of interest were diabetes, hyperglycemia, measures of anthropometry, cardiovascular disease (CVD) and hypertension. Data were extracted and meta-analyzed when feasible, using a random-effects model. Thirty-three studies with sample size ranging from 239 to 4811 met the inclusion criteria, including five with a prospective design. Twelve studies reported on diabetes or hyperglycemia, 16 on anthropometry, 6 on CVD and 3 on hypertension. Evidence for a positive association between uBPA concentrations and diabetes, overweight, obesity, elevated waist circumference (WC), CVD and hypertension was found in 7/8, 2/7, 6/7, 5/5, 4/5 and 2/3 of the cross-sectional studies, respectively. We were able to conduct outcome-specific meta-analyses including 12 studies. When comparing the highest vs. the lowest uBPA concentrations, the pooled ORs were 1.47 (95% CI: 1.21-1.80) for diabetes, 1.21 (95% CI: 0.98-1.50) for overweight, 1.67 (95% CI: 1.41-1.98) for obesity, 1.48 (95% CI: 1.25-1.76) for elevated WC, and 1.41 (95% CI: 1.12-1.79) for hypertension. Moreover, among the five prospective studies, 3 reported significant findings, relating BPA exposure to incident diabetes, incident coronary artery disease, and weight gain. To conclude, there is evidence from the large body of cross-sectional studies that individuals with higher uBPA concentrations are more likely to suffer from diabetes, general/abdominal obesity and hypertension than those with lower uBPA concentrations. Given the potential importance for public health, prospective cohort studies with proper adjustment for dietary characteristics and identification of critical windows of exposure are urgently needed to further improve knowledge about potential causal links between BPA exposure and the development of chronic disease.