Yona Amitai

Phthalate exposure among pregnant women in Jerusalem, Israel: Results of a pilot study

BACKGROUND Phthalates can disrupt endocrine function and induce reproductive and developmental toxicity in laboratory animals. Few studies have evaluated exposure to phthalates in pregnant women, despite the potential sensitivity of the developing fetus to adverse effects of phthalates. METHODS We measured urinary concentrations of 11 phthalate metabolites in 19 pregnant women, recruited in Jerusalem, Israel in 2006, and collected questionnaire data on demographic factors and consumer habits from these women. We compared geometric mean concentrations in subgroups and used the Mann-Whitney U-test for independent samples to determine significant differences between groups. RESULTS Nine metabolites were detected in at least 95% of the samples: mono(2-ethyl-5-carboxypentyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, mono(3-carboxypropyl) phthalate, mono(n-butyl) phthalate, monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), mono(2-ethylhexyl) phthalate and monoisobutyl phthalate. Phthalate metabolite concentrations in these pregnant women were remarkably similar to those in the general United States female population. MBzP geometric mean concentrations were higher in women living in buildings existing 40 years or more (P=0.04). In women who used four or more personal care products (perfume, deodorant, lipstick, nail polish, or hand/face cream) in the 48 h prior to providing the urine sample, geometric mean MEP concentrations were more than 4 times higher than concentrations in women using only two or three of the aforementioned products (P=0.07). CONCLUSIONS Pregnant women in Jerusalem are exposed to a wide range of phthalates. Building materials used in old constructions may be a source of exposure to benzylbutyl phthalate, the parent compound of MBzP. Personal care products may be sources of exposure to diethyl phthalate, the parent compound of MEP.

Air pollution and congenital heart defects.

Environmental factors such as ambient air pollution have been associated with congenital heart defects. The aim of this study was to investigate the association between gestational exposure to air pollution and the risk of congenital heart defects. We conducted a registry-based cohort study with a total of 135,527 live- and still-births in the Tel-Aviv region during 2000-2006. We used a Geographic Information System-based spatiotemporal approach with weekly inverse distance weighting modeling to evaluate associations between gestational exposure to ambient air pollution during weeks 3-8 of pregnancy and the risk for congenital heart defects. The following pollutants were studied: carbon monoxide, nitrogen-dioxide, ozone, sulfur-dioxide and particulate matter with aerodynamic diameter smaller than 10 μm and 2.5 μm (PM10, PM2.5 respectively). Logistic models, adjusted for socio-demographic covariates were used to evaluate the associations. We found that maternal exposure to increased concentrations of PM10 was associated with multiple congenital heart defects (adjusted OR 1.05, 95% CI: 1.01 to 1.10 for 10 μg/m(3) increment). An inverse association was observed between concentrations of PM2.5 and isolated patent ductus arteriosus (adjusted OR 0.78, 95% CI: 0.68 to 0.91 for 5 µg/m(3) increment). Sensitivity analyses showed that results were consistent. Generally there were no evidence for an association between gaseous air pollutants and congenital heart defects.Our results for PM10 and congenital heart defects confirm results from previous studies. The results for PM2.5 need further investigations.

Green spaces and adverse pregnancy outcomes

Objective The objective of this study was to evaluate the associations between proximity to green spaces and surrounding greenness and pregnancy outcomes, such as birth weight, low birth weight (LBW), very LBW (VLBW), gestational age, preterm deliveries (PTD) and very PTD (VPTD). Methods This study was based on 39 132 singleton live births from a registry birth cohort in Tel Aviv, Israel, during 2000–2006. Surrounding greenness was defined as the average of satellite-based Normalised Difference Vegetation Index (NDVI) in 250 m buffers and proximity to major green spaces was defined as residence within a buffer of 300 m from boundaries of a major green space (5000 m2), based on data constructed from OpenStreetMap. Linear regression (for birth weight and gestational age) and logistic regressions models (for LBW, VLBW, PTD and VPTD) were used with adjustment for relevant covariates. Results An increase in 1 interquartile range greenness was associated with a statistically significant increase in birth weight (19.2 g 95% CI 13.3 to 25.1) and decreased risk of LBW (OR 0.84, 95% CI 0.78 to 0.90). Results for VLBW were in the same direction but were not statistically significant. In general, no associations were found for gestational age, PTD and VPTD. The findings were consistent with different buffer and green space sizes and stronger associations were observed among those of lower socioeconomic status. Conclusions This study confirms the results of a few previous studies demonstrating an association between maternal proximity to green spaces and birth weight. Further investigation is needed into the associations with VLBW and VPTD, which has never been studied before.

Urinary concentrations of organophosphate pesticide metabolites in adults in Israel: demographic and dietary predictors.

Exposure to organophosphate pesticides (OPs) in agricultural and urban populations has been associated with a range of adverse health effects. The purpose of the current study was to estimate exposure to OPs in the general adult population in Israel and to determine dietary and demographic predictors of exposure. We measured six non-specific organophosphate pesticide metabolites (dialkyl phosphates) in urine samples collected from 247 Israeli adults from the general population. We collected detailed demographic and dietary data from these individuals, and explored associations between demographic and dietary characteristics and urinary dialkyl phosphate concentrations. OP metabolites were detectable in all urine samples. Concentrations of several dialkyl phosphate metabolites (dimethylphosphate, dimethylthiophosphate, diethylphosphate) were high in our study population relative to the general populations in the US and Canada and were comparable to those reported in 2010 in France. Total dialkyl phosphates were higher in individuals with fruit consumption above the 75th percentile. In a multivariate analysis, total molar dialkyl phosphate concentration increased with age and was higher in individuals with high income compared to individuals with the lowest income. Total diethyl metabolite concentrations were higher in females and in study participants whose fruit consumption was above the 75th percentile. In conclusion, we found that levels of exposure to OP pesticides were high in our study population compared to the general population in the US and Canada and that intake of fruits is an important source of exposure.

Relative prevalence of malformations at birth among different religious communities in Israel.

The aim of this research was to determine the relative prevalence at birth of major malformations among the different religious communities in Israel as a way to better understand their causes. We collected data on malformations present among liveborn infants in a 10‐year period from the national registry of birth defects according to the religious affiliation. In a total of 1,203,763 liveborn infants, the prevalence of major malformations was in a similar range among Jews and Christians and much higher among Muslim and Druze. These observations may be explained by differences between these communities, in particular, the rates of consanguinity and of therapeutic abortions. The Muslim and Druze communities in Israel are those with the highest consanguinity rates and the lowest rates of termination of pregnancies when a malformation is diagnosed. Analysis of the differences in the rate of malformations at birth in different communities is important for Public Health planning. It may also help to delineate causes and serve as the basis for research.

Urinary concentrations of environmental contaminants and phytoestrogens in adults in Israel

BACKGROUND The Ministry of Health Biomonitoring Study estimated exposure of individuals in the Israeli population to bisphenol A (BPA), organophosphate (OP) pesticides, phthalates, cotinine, polycyclic aromatic hydrocarbons (PAHs), and the phytoestrogenic compounds genistein and daidzein. METHODS In 2011, 250 individuals (ages 20-74) were recruited from five different regions in Israel. Urine samples were collected and questionnaire data were obtained, including detailed dietary data (food frequency questionnaire and 24hour recall). Urinary samples were analyzed for BPA, OP metabolites (dialkyl phosphates), phthalate metabolites, cotinine, PAH metabolites, genistein, and daidzein. RESULTS AND DISCUSSION BPA urinary concentrations were above the limit of quantification (LOQ) in 89% of the samples whereas urinary concentrations of phthalate metabolites were above the LOQ in 92-100% of the samples. PAH metabolites were above the LOQ in 63-99% of the samples whereas OP metabolites were above the LOQ in 44-100% of the samples. All non-smoking participants had detectable levels of cotinine in their urine; 63% had levels above the LOQ, and the rate of quantification was high compared to the general non-smoking population in Canada. Median creatinine adjusted concentrations of several OP metabolites (dimethyl phosphate, dimethyl thiophosphate) were high in our study population compared to the general US and Canadian populations. Median creatinine adjusted urinary BPA concentrations in the study population were comparable to those in Belgium and Korea; higher than those reported for the general US, German, and Canadian populations; and very low compared to health-based threshold values. Phthalate concentrations were higher in our study population compared to the general US population but values were very low compared to health-based threshold values. Median creatinine adjusted PAH concentrations were generally comparable to those reported for the general US population; median creatinine adjusted daidzein concentrations were high in our population compared to the general US population whereas genistein concentrations were comparable. CONCLUSIONS We interpreted observed urinary contaminant levels observed in our study by comparing values with health-based threshold values and/or values from international human biomonitoring studies. Using this data interpretation scheme, we identified two contaminants as being of potential public health concern and high priority for public health policy intervention: environmental tobacco smoke (ETS) and OP pesticides. We used the data collected in this study to support public health policy interventions. We plan to conduct a follow-up biomonitoring study in 2015 to measure ETS and OP exposure in the general population in Israel, to evaluate the effectiveness of relevant policy interventions.

Folic acid supplementation for pregnant women and those planning pregnancy: 2015 update

During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid–sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4‐1.0 mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7 mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3‐ to 5‐fold higher in Northern China and 3‐fold higher in India. A recent population‐based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with known genetic variations in the folate metabolic cycle, those exposed to medications with antifolate effects, smokers, diabetics, and the obese may benefit from higher doses of folic acid daily during the first trimester.

Urinary concentrations of polycyclic aromatic hydrocarbons in Israeli adults: Demographic and life-style predictors

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants associated with adverse health outcomes, including cancer, asthma, and reduced fertility. Because data on exposure to these contaminants in Israel and the Middle East are very limited this study was conducted to measure urinary levels of PAHs in the general adult population in Israel and to identify demographic and life-style predictors of exposure. We measured concentrations of five PAH metabolites: 1-hydroxypyrene (1OH_pyrene) and four different hydroxyphenanthrenes (1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene), as well as cotinine in urine samples collected from 243 Israeli adults from the general population. We interviewed participants using structured questionnaires to collect detailed demographic, smoking and dietary data. For over 99% of the study participants, urinary concentration of at least one of the PAHs was above both the limit of detection (LOD) and the limit of quantification (LOQ). All PAHs were significantly correlated (rho=0.67-0.92). Urinary concentration of hydroxyphenanthrenes, but not 1OH_pyrene, was significantly higher among Arabs and Druze study participants (N=56) compared to Jewish participants (N=183). For 4-hydroxyphenanthrene, concentration in Arabs and Druze was 1.95 (95% CI 1.50-2.52) that of Jews, after controlling for creatinine, age and cotinine levels. Urinary concentrations of all PAHs were significantly higher among current smokers or participants with higher cotinine levels and increased significantly with smoking frequency. While PAHs concentrations were not associated with cotinine concentrations in nonsmokers in the overall study population, PAHs concentration was significantly higher among nonsmoking Jews with cotinine ≥LOQ (1μg/L), which represents exposure to environmental tobacco smoking, compared to nonsmoking Jews with cotinine concentrations <LOQ, with the highest ratio for 1OH_pyrene (Ratio=2.38, 95% CI 1.47-3.85). Among nonsmoking Arabs and Druze, higher hydroxyphenanthrenes concentrations were found for those consuming grilled food once a month or more. For 3-hydroxyphenanthrene, concentration in those consuming grilled food once a month or more was 2.72 (95% CI 1.01-4.98) times that of those consuming grilled food less than once a month or not at all, after controlling for creatinine, age and cotinine levels. In conclusion, we found that the general adult population in Israel is widely exposed to PAHs. Exposure differed by ethnic sub-groups both in magnitude and sources of exposure. The finding of higher exposure among Arabs and Druze highlights disparities in environmental exposures across subpopulations and suggests that further research and preventive measure are warranted to reduce PAHs exposure and associated health outcomes, especially in the Arab population in the Middle East.

Anemia and Iron Deficiency in Children: Association With Red Meat and Poultry Consumption

Objective: The aim of this study was to study the relative contribution of dietary sources of iron in children with high prevalence of anemia and iron deficiency (ID). Methods: A cross-sectional study in 263 healthy, 1.5- to 6-year-old children in the Jewish sector of Jerusalem, Israel. Venous blood samples and a qualitative Food Frequency Questionnaire on iron-rich foods were obtained. Anemia was defined as hemoglobin <11 g/dL for children younger than 4 years and <11.5 g/dL for children older than 4 years; ID was defined as ferritin <12 &mgr;g/L. Results: Anemia was found in 11.2%, ID in 22%, and iron-deficiency anemia in 3.7%. The prevalence of anemia was higher in toddlers ages 1.5 to 3 years compared with children ages 3 to 6 years (17.7% vs 7.3%, P = 0.01). Children with extremely low red meat consumption (seldom) had 4-fold higher rates of ID than those who consumed ≥2 times per week (odds ratio 3.98; 95% confidence interval 1.21–13.03; P = 0.023), whereas poultry consumption was not associated with ID. Soy consumption was inversely associated with ferritin (marginally significant, r = −0.134, P = 0.057). Conclusions: The high prevalence of anemia and ID found in this study, mainly in children 1.5 to 3 years old, is related to low red meat consumption. The characteristically high poultry consumption in the Israeli population was not protective. The shift toward reduced red meat consumption and higher poultry consumption in developed countries may result in increasing the risk of ID.

Desalinated seawater supply and all-cause mortality in hospitalized acute myocardial infarction patients from the Acute Coronary Syndrome Israeli Survey 2002–2013

BACKGROUND Consuming desalinated seawater (DSW) as drinking water (DW) may reduce magnesium in water intake causing hypomagnesemia and adverse cardiovascular effects. METHODS We evaluated 30-day and 1-year all-cause mortality of acute myocardial infarction (AMI) patients enrolled in the biannual Acute Coronary Syndrome Israeli Survey (ACSIS) during 2002-2013. Patients (n=4678) were divided into 2 groups: those living in regions supplied by DSW (n=1600, 34.2%) and non-DSW (n=3078, 65.8%). Data were compared between an early period [2002-2006 surveys (n=2531) - before desalination] and a late period [2008-2013 surveys (n=2147) - during desalination]. RESULTS Thirty-day all-cause-mortality was significantly higher in the late period in patients from the DSW regions compared with those from the non-DSW regions (HR=2.35 CI 95% 1.33-4.15, P<0.001) while in the early period there was no significant difference (HR=1.37 CI 95% 0.9-2, P=0.14). Likewise, there was a significantly higher 1-year all-cause mortality in the late period in patients from DSW regions compared with those from the non-DSW regions (HR=1.87 CI 95% 1.32-2.63, P<0.0001), while in the early period there was no significant difference (HR=1.17 CI 95% 0.9-1.5, P=0.22). Admission serum magnesium level (M±SD) in the DSW regions (n=130) was 1.94±0.24mg/dL compared with 2.08±0.27mg/dL in 81 patients in the non-DSW (P<0.0001). CONCLUSIONS Higher 30-day and 1-year all-cause mortality in AMI patients, found in the DSW regions may be attributed to reduced magnesium intake secondary to DSW consumption.