Risk and protective factors for breast cancer (BC) include lifestyle, diet, reproduction, and others. Increased risk for colon cancer was linked with low water intake. The link between water consumption and BC was scarcely studied. We investigated the association between water and fluid consumption and the occurrence of BC in a retrospective case–control study in the Shaare Zedek Medical Center, Jerusalem, in 206 women aged 25–65 years (106 with newly diagnosed BC, and 100 controls). A food frequency questionnaire (FFQ), consumption of water, foods, and beverages, lifestyle, and other risk and protective factors were recorded. The age of women in both groups was comparable ((M ± SD) 52.7 ± 9.8 and 50.6 ± 11.4 years, respectively (p = 0.29)). Women with BC consumed 20.2% less water (M ± SD=5.28 ± 4.2 and 6.62 ± 4.5 cups/day, respectively, p = 0.02) and 14% less total fluids than controls (M ± SD=2095 ± 937 mL/day and 2431 ± 1087 mL/day, respectively, p = 0.018). Multiple stepwise logistic regression showed that the differences remained significant both for daily water consumption (p = 0.031, CI = 0.462–0.964) and for total daily liquid intake (p = 0.029, CI = 0.938–0.997). Low water and liquids intake as a risk factor for BC may be related to the younger age of our subjects. The effect of age on the potential role of water intake in decreasing BC risk should be investigated.

Background: There is an increasing awareness to ankyloglossia (tongue-tie) in infants, with marked increase in its report in the medical literature. Some reports indicate increase in prevalence. Whether the increase ankyloglossia rate is a real phenomenon or merely reflects increased awareness and reports has to be determined. One explanation for the increasing ankyloglossia rates is the growing trend of breast feeding initiation, often impaired by ankyloglossia, which brings it to medical attention. We propose an alternative hypothetical explanation based on increasing utilization of periconceptional folic acid supplementation for the prevention of neural tube defects (NTDs). Inadequate folic acid supply during organogenesis impairs cell division, and the mid-line structures are at the highest risk. We postulated that higher folic acid supply during organogenesis might enhance tissue synthesis with tighter closure of mid-line structures including the lingual frenulum, resulting in ankyloglossia. Methods: To assess this hypothesis, we undertook an observational case control study comparing folic acid utilization before pregnancy in mothers of infants with and without ankyloglossia. Infants with ankyloglossia (n = 85) were compared to a control group without ankyloglossia (n = 140). Results: There was a slight, insignificant elevated frequency of reported utilization of folic acid ("any intake") among mothers of infants with ankyloglossia compared with controls (74.1% and 66.4%, respectively). This difference was slightly higher, yet insignificant when folic acid intake "in most days" was considered (65.9% and 53.6%, respectively, OR = 1.67, 95%CI = 0.93-3.05, P = 0.07). In contrast, the reported intake of pre-conceptional folic acid "on a regular basis" was significantly higher among mothers of infants with ankyloglossia compared with controls (54.1% and 25.7%, respectively, OR = 3.41, 95% CI = 1.85-6.27, p < 0.0001). Interpretation: The reported association between higher frequency of regular pre-conceptional folic acid intake and ankyloglossia, supports the hypothesis for this association. More studies are required to test this hypothesis.

Drinking water (DW) is an important dietary source of magnesium. Israel has recently increased desalinated seawater (DSW) production for DW, but negligible magnesium content in DSW may pose a risk of hypomagnesemia and consequential adverse cardiovascular effects. Consecutive acute myocardial infarction (AMI) patients (n = 380, age 35-75 years), hospitalized in 2015-2017 with ST-segment elevation myocardial infarction (STEMI), were divided into two groups based on their domicile region having a major supply of DSW (n = 250, 65%) or not (non-DSW; n = 130, 35%). We evaluated admission serum magnesium concentrations in patients, magnesium levels in tap water, 1-year all-cause mortality, and major adverse cardiovascular events (MACE), including all-cause mortality, nonfatal myocardial infarction, rehospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions. Multivariate analyses were adjusted for age and sex. Serum magnesium concentrations (mean ± SD) were significantly higher among patients in the non-DSW group compared with the DSW group (1.95 ± 0.20 mg/dL and 1.81 ± 0.20 mg/dL, P < 0.001; respectively). Additionally, the mean residential DW magnesium level in the DSW group was 5.4 ± 2.2 mg/L compared with 25.1 ± 3.4 mg/L, P < 0.01 in the non-DSW group. Fewer patients (although not statistically significant) in the non-DSW group experienced major adverse cardiovascular events (MACE) or 1-year-all-cause mortality compared with the patients in the DSW group (12.4% and 20%, P = 0.065; respectively). In conclusion, in post AMI patients, we found nonsignificant higher MACE and 1-year mortality with the use of DSW.

OBJECTIVES:Orofacial clefts are one of the most common birth malformations and represent a significant public health economic expenditure. The purpose of this investigation was to study the epidemiology of orofacial clefts in newborns from 1993 to 2005 in Israel. In addition, a comparison of data from the National Birth Defects Registry (NBDR) and Hospital records will be made.METHODS:A retrospective data review of reports to the Israeli NBDR on infants with orofacial clefts in comparison with records reviewed at 13 major hospitals, accounting for 60% of all births in Israel.RESULTS:Of 1334 newborns found to be with orofacial clefts all over Israel between 1993 and 2005, 1015 were reported to the NBDR and 319 were unreported but retrieved from hospital files. During this period, of the 976 578 live births found in the 13 participating hospitals, there were 866 newborns with orofacial clefts. Of those, 684 (79%) were nonsyndromic orofacial clefts and 182 (21%) had additional syndromes. The prevalence of nonsyndromic orofacial clefts was 7/10 000 live births, lower than reported outside Israel. Only 65% of orofacial clefts retrieved from the 13 hospitals were reported to the NBDR. A significantly higher orofacial cleft prevalence was found among non-Jews than Jews (11 and 6 of 10 000 live births, respectively), (P < .00 001). CL/P was found more frequently than isolated cleft palate (CP). More males had orofacial clefts than females, mostly unilateral with left side predominance.CONCLUSIONS:The prevalence of nonsyndromic orofacial clefts was found to be 7/10 000 live births. The higher orofacial cleft prevalence among non-Jews may be explained by the high prevalence of consanguinity and deprived maternal nutritional status in this population.

Background: Neural tube defects (NTDs) affect > 300,000 children annually worldwide. The incidence of NTDs in Northern India (7.7/1000), is tenfold higher than in the US (0.7/1000). Higher rates were previously reported in Northern China. The causes of these trends have not been elucidated. Arsenic is a teratogen shown in animals to induce NTDs. The main potential sources for environmental arsenic exposure, groundwater and rice as a staple food, are high in India and China. Objectives: To discuss the possible association between high environmental arsenic exposure through drinking water and rice with the high NTDs rates in these regions. Discussion: Arsenic contamination of groundwater is the main source of environmental arsenic exposure. The locations of toxic arsenic regions in China and India correspond in most cases to the northern regions where the NTDs rates were high. Rice, the staple food in India and China, can absorb up to 10 times more arsenic than other crops, such as wheat and might further increase arsenic exposure. Conclusions: We hypothesize that this NTD-arsenic in drinking water and rice association may explain why these areas in the northern regions of both countries have the highest incidence of NTDs. If proven true, this has major public health implications.

Background: In 2010, Médecins Sans Frontières (MSF) discovered extensive lead poisoning impacting several thousand children in rural northern Nigeria. An estimated 400 fatalities had occurred over 3 mo. The US Centers for Disease Control and Prevention (CDC) confirmed widespread contamination from lead-rich ore being processed for gold, and environmental management was begun. MSF commenced a medical management programme that included treatment with the oral chelating agent 2,3-dimercaptosuccinic acid (DMSA, succimer). Here we describe and evaluate the changes in venous blood lead level (VBLL) associated with DMSA treatment in the largest cohort of children #5 y of age with severe paediatric lead intoxication reported to date to our knowledge. Methods and Findings: In a retrospective analysis of programme data, we describe change in VBLL after DMSA treatment courses in a cohort of 1,156 children #5 y of age who underwent between one and 15 courses of chelation treatment. Courses of DMSA of 19 or 28 d duration administered to children with VBLL $ 45 mg/dl were included. Impact of DMSA was calculated as end-course VBLL as a percentage of pre-course VBLL (ECP). Mixed model regression with nested random effects was used to evaluate the relative associations of covariates with ECP. Of 3,180 treatment courses administered, 36% and 6% of courses commenced with VBLL $ 80 mg/dl and $ 120 mg/dl, respectively. Overall mean ECP was 74.5% (95% CI 69.7%–79.7%); among 159 inpatient courses, ECP was 47.7% (95% CI 39.7%–57.3%). ECP after 19-d courses (n = 2,262) was lower in older children, first-ever courses, courses with a longer interval since a previous course, courses with more directly observed doses, and courses with higher pre-course VBLLs. Low haemoglobin was associated with higher ECP. Twenty children aged #5 y who commenced chelation died during the period studied, with lead poisoning a primary factor in six deaths. Monitoring of alanine transaminase (ALT), creatinine, and full blood count revealed moderate ALT elevation in ,2.5% of courses. No clinically severe adverse drug effects were observed, and no laboratory findings required discontinuation of treatment. Limitations include that this was a retrospective analysis of clinical data, and unmeasured variables related to environmental exposures could not be accounted for. Conclusions: Oral DMSA was a pharmacodynamically effective chelating agent for the treatment of severe childhood lead poisoning in a resource-limited setting. Re-exposure to lead, despite efforts to remediate the environment, and nonadherence may have influenced the impact of outpatient treatment. Please see later in the article for the Editors’ Summary. Citation: Thurtle N, Greig J, Cooney L, Amitai Y, Ariti C, et al. (2014) Description of 3,180 Courses of Chelation with Dimercaptosuccinic Acid in Children #5 y with Severe Lead Poisoning in Zamfara, Northern Nigeria: A Retrospective Analysis of Programme Data. PLoS Med 11(10): pmed.1001739. doi:10.1371/journal.pmed.1001739 Academic Editor: Bruce P Lanphear, Simon Fraser University, Canada Received September 16, 2013; Accepted August 19, 2014; Published October 7, 2014 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Data Availability: The authors confirm that, for approved reasons, some access restrictions apply to the data underlying the findings. Research data are accessible via the MSF open data policy for researchers who meet the criteria for access to confidential data (http://fieldresearch.msf.org/msf/handle/10144/306501). Funding: This study was funded as part of MSF operations. Lundbeck donated some DMSA, but had no role in the treatment programme or in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The findings and conclusions in this presentation have not been formally disseminated by the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry and should not be construed to represent any agency determination or policy. Competing Interests: The authors have declared that no competing interests exist. Abbreviations: ALT, alanine transaminase; BD, twice daily; CaNa2EDTA, calcium disodium versenate; CDC, US Centers for Disease Control and Prevention; DMSA, 2,3-dimercaptosuccinic acid; DOT, directly observed therapy; ICPMS, inductively coupled plasma mass spectrometry; IV, intravenous; ECP, end-course venous blood lead level as a percentage of pre-course venous blood lead level; MSF, Médecins Sans Frontières; TDS, thrice daily; VBLL, venous blood lead level. * Email: Jane.Greig@london.msf.org PLOS Medicine | www.plosmedicine.org 1 October 2014 | Volume 11 | Issue 10 | pmed.1001739

In Israel, about 55% of drinking water is derived from desalination (DSW) which removes all iodine. A recent study from Israel demonstrated high rates of iodine deficiency among school-aged children and pregnant women. There are concerns that low iodine may lead to impaired thyroid function. However, to date, the impact of consuming DSW on body iodine status has not been studied. The objective was to assess whether the increased use of DSW is associated with increased rates of hypothyroidism. Using data from a large health fund in Israel, we compared proportions of patients with higher than normal thyroid stimulating hormone (TSH), and lower than normal T3 and T4 levels before and after a massive desalination project became operational in August 2013 in areas with high vs. low use of DSW. Over 400,000 cases were compared in 2010-2013 vs. 2014-2016. Overall, there was no increase in the proportion of individuals with higher than normal TSH levels, or lower than normal T3 and T4 levels. In conclusion, in this population-based study, following the introduction of DSW, there was no evidence of increased incidence of low thyroid function tests, and the trends were similar in both areas highly consuming, or not consuming, DSW.

BACKGROUND:Drinking water (DW) is an important dietary source of magnesium. Recently, Israel has increased its use of desalinated seawater (DSW) as DW country-wide. Its negligible magnesium content, however, raises concern that consumption of DSW may be associated with hypomagnesemia and increase the risk of ischemic heart disease (IHD), diabetes mellitus (DM), and colorectal cancer (CRC).OBJECTIVES:We tested whether there was a change in incidence of negative health outcomes (IHD, DM, and CRC) following the introduction of DSW supply in a population-based ecologic study in Israel.METHODS:A historical prospective analysis was applied to members aged 25-76 during 2004-2013 of Clalit Health Services (Clalit), the largest healthcare provider in Israel, using its electronic medical record database. Multivariable analyses were adjusted for age, sex, socioeconomic status, smoking status, and body mass index.RESULTS:An increased odds ratio was found for IHD (0.96, 95% CI 0.93-0.99 at baseline and 1.06, 95% CI 1.02-1.11 at the end of the follow-up period), but no time trend was observed.CONCLUSIONS:We found that the risk for IHD increased during the study period. The risks for DM and CRC were unchanged. Long term studies are needed for assessing the risk for CRC due to the long latency. The higher risk for IHD has practical public health implications and raise the need to add magnesium to DSW.

With increasing shortage of fresh water globally, more countries are consuming desalinated seawater (DSW). In Israel >50% of drinking water is now derived from DSW. Desalination removes magnesium, and hypomagnesaemia has been associated with increased cardiac morbidity and mortality. Presently the impact of consuming DSW on body magnesium status has not been established. We quantified changes in serum magnesium in a large population based study (n = 66,764), before and after desalination in regions consuming DSW and in regions where DSW has not been used. In the communities that switched to DSW in 2013, the mean serum magnesium was 2.065 ± 0.19 mg/dl before desalination and fell to 2.057 ± 0.19 mg/dl thereafter (p < 0.0001). In these communities 1.62% of subjects exhibited serum magnesium concentrations ≤1.6 mg/dl between 2010 and 2013. This proportion increased by 24% between 2010-2013 and 2015-2016 to 2.01% (p = 0.0019). In contrast, no such changes were recorded in the communities that did not consume DSW. Due to the emerging evidence of increased cardiac morbidity and mortality associated with hypomagnesaemia, it is vital to consider re-introduction of magnesium to DSW.

Background: Children's aversions to poor and mostly bitter tastes and their inability to swallow tablets and capsules are major challenges in pediatric medicine. Sodium phenylbutyrate (NaPB) is a lifesaving waste nitrogen, alternative to urea nitrogen, for individuals suffering from urea cycle disorders. A major issue in the use of NaPB is its highly foul taste, which often leads to children being unable to consume it, resulting in ineffective treatment, or alternatively, necessitating the application of the drug through a nasogastric tube or gastrostomy.Methods: This study reviews the published data on a novel formulation of NaPB, Pheburane((R)) granules, which begin to release their NaPB after a lag time of similar to 10 seconds followed by a slow release over several minutes.Results: The taste-masked granule formulation of NaPB dramatically improves the acceptability of the drug by children and appears in initial studies to be both safe and effective.Conclusion: While more studies are needed to substantiate and enrich these initial trials, the available data provide a telling example where masking the drug taste of medicine for children can sometimes be the difference between life and death.

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 +/- 0.24 mg/dL compared with 2.08 +/- 0.27 mg/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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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.

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Pediatric primary care is the cornerstone of health care services for children. Performance of common office procedures is an integral part of primary care. Ideally, the community-based primary care pediatrician provides comprehensive health care services and only refers a small minority of patients for consultation. However, knowledge regarding Israeli pediatricians’ practices of office procedures is scant.

Women were classified as periconcep-tionaluse(frombeforethelastmenstrualperiodbeforeconceptionuntiltheendofthefirsttrimester),lateuse(startingfolicacidsupplementationduringthefirsttri-mester,sometimeafterthelastmenstrualperiod),andearly discontinuation of folic acid (those with no peri-conceptionalfolicaciduse).Without folic acid, the rates of NTDs were 4.8 in1000and1.0in1000inthenorthernandsouthernre-gions,respectively.Withpericonceptionalfolicaciduse,NTDratesdroppedto1.0in1000and0.6in1000inthenorthernandsouthernregions,respectively.TheratesofNTDsamong129 923pregnanciesshowedthat“lateuse”alsowasassociatedwithamarkeddecreaseinNTDrates, as compared with “early discontinuation” (1.6 in1000 vs 3.3 in 1000 in the northern region and 0.7 in1000vs1.1in1000inthesouthernregion).

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, 3hydroxyphenanthrene, 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 ofJews, 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 (1 mu g/L), which represents exposure to environmental tobacco smoking, compared to nonsmoking Jews with cotinine concentrations <LOQ with the highest ratio for 10H_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. (C) 2014 Elsevier GmbH. All rights reserved.

BACKGROUND:Orofacial clefts are the most common craniofacial congenital malformations, with significant anatomic, ethnic, racial and gender differences.OBJECTIVES:To investigate the prevalence, distribution and characteristic features of various types of non-syndromic clefts among Israeli Jews and Arabs.METHODS:We conducted a retrospective multi-center survey in 13 major hospitals in Israel for the period 1993-2005. To obtain the true prevalence and detailed clinical characteristics, data on liveborn infants with non-syndromic clefts were obtained from the Ministry of Health's National Birth Defect Registry and completed by chart reviews in the 13 surveyed hospitals.RESULTS:Of 976,578 liveborn infants, 684 presented unilateral or bilateral clefts, with a prevalence of 7.00/10,000 live births; 479 were Jews and 205 were Arabs. The prevalence was higher among Arabs compared to Jews (11.12 and 6.22 per 10,000 live births in Arabs and Jews, respectively, P 0.00001). Males had higher cleft rates than females (7.69/10,000 and 6.17/10,000 live births, respectively, P = 0.05). Males had more cleft lips (P < 0.05) and cleft lips with cleft palate (P < 0.001). There was left-side predominance. Newborns of younger mothers (age < 20 years) and of older mothers (age ≥ 45 years) had higher cleft rates than those with mothers in the 20-44 year bracket (P < 0.009). Children born at or above the 5th birth order had a higher cleft rate (P < 0.001).CONCLUSIONS:The prevalence of non-syndromic clefts was 7.00/10,000 live births. The markedly higher rate in Arabs is related to the high rate of consanguinity. Both very young and old maternal age represents a higher risk of clefts in their offspring.

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 m(2)), 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.

BACKGROUND:In 2010, Médecins Sans Frontières (MSF) discovered extensive lead poisoning impacting several thousand children in rural northern Nigeria. An estimated 400 fatalities had occurred over 3 mo. The US Centers for Disease Control and Prevention (CDC) confirmed widespread contamination from lead-rich ore being processed for gold, and environmental management was begun. MSF commenced a medical management programme that included treatment with the oral chelating agent 2,3-dimercaptosuccinic acid (DMSA, succimer). Here we describe and evaluate the changes in venous blood lead level (VBLL) associated with DMSA treatment in the largest cohort of children ≤ 5 y of age with severe paediatric lead intoxication reported to date to our knowledge.METHODS AND FINDINGS:In a retrospective analysis of programme data, we describe change in VBLL after DMSA treatment courses in a cohort of 1,156 children ≤ 5 y of age who underwent between one and 15 courses of chelation treatment. Courses of DMSA of 19 or 28 d duration administered to children with VBLL ≥ 45 µg/dl were included. Impact of DMSA was calculated as end-course VBLL as a percentage of pre-course VBLL (ECP). Mixed model regression with nested random effects was used to evaluate the relative associations of covariates with ECP. Of 3,180 treatment courses administered, 36% and 6% of courses commenced with VBLL ≥ 80 µg/dl and ≥ 120 µg/dl, respectively. Overall mean ECP was 74.5% (95% CI 69.7%-79.7%); among 159 inpatient courses, ECP was 47.7% (95% CI 39.7%-57.3%). ECP after 19-d courses (n = 2,262) was lower in older children, first-ever courses, courses with a longer interval since a previous course, courses with more directly observed doses, and courses with higher pre-course VBLLs. Low haemoglobin was associated with higher ECP. Twenty children aged ≤ 5 y who commenced chelation died during the period studied, with lead poisoning a primary factor in six deaths. Monitoring of alanine transaminase (ALT), creatinine, and full blood count revealed moderate ALT elevation in <2.5% of courses. No clinically severe adverse drug effects were observed, and no laboratory findings required discontinuation of treatment. Limitations include that this was a retrospective analysis of clinical data, and unmeasured variables related to environmental exposures could not be accounted for.CONCLUSIONS:Oral DMSA was a pharmacodynamically effective chelating agent for the treatment of severe childhood lead poisoning in a resource-limited setting. Re-exposure to lead, despite efforts to remediate the environment, and non-adherence may have influenced the impact of outpatient treatment. Please see later in the article for the Editors' Summary.