Eva-Charlotte Ekström

Arsenic Exposure During Pregnancy and Size at Birth: A Prospective Cohort Study in Bangladesh

The authors evaluated the association of prenatal arsenic exposure with size at birth (birth weight, birth length, head and chest circumferences). This prospective cohort study, based on 1,578 mother-infant pairs, was conducted in Matlab, Bangladesh, in 2002-2003. Arsenic exposure was assessed by analysis of arsenic in urine collected at around gestational weeks 8 and 30. The association of arsenic exposure with size at birth was assessed by linear regression analyses. In analysis over the full range of exposure (6-978 microg/L), no dose-effect association was found with birth size. However, significant negative dose effects were found with birth weight and head and chest circumferences at a low level of arsenic exposure (<100 microg/L in urine). In this range of exposure, birth weight decreased by 1.68 (standard error (SE), 0.62) g for each 1-microg/L increase of arsenic in urine. For head and chest circumferences, the corresponding reductions were 0.05 (SE, 0.03) mm and 0.14 (SE, 0.03) mm per 1 microg/L, respectively. No further negative effects were shown at higher levels of arsenic exposure. The indicated negative effect on birth size at a low level of arsenic exposure warrants further investigation.

Exclusive breastfeeding promotion by peer counsellors in sub-Saharan Africa (PROMISE-EBF): a cluster-randomised trial

BACKGROUND Exclusive breastfeeding (EBF) is reported to be a life-saving intervention in low-income settings. The effect of breastfeeding counselling by peer counsellors was assessed in Africa. METHODS 24 communities in Burkina Faso, 24 in Uganda, and 34 in South Africa were assigned in a 1:1 ratio, by use of a computer-generated randomisation sequence, to the control or intervention clusters. In the intervention group, we scheduled one antenatal breastfeeding peer counselling visit and four post-delivery visits by trained peers. The data gathering team were masked to the intervention allocation. The primary outcomes were prevalance of EBF and diarrhoea reported by mothers for infants aged 12 weeks and 24 weeks. Country-specific prevalence ratios were adjusted for cluster effects and sites. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00397150. FINDINGS 2579 mother-infant pairs were assigned to the intervention or control clusters in Burkina Faso (n=392 and n=402, respectively), Uganda (n=396 and n=369, respectively), and South Africa (n=535 and 485, respectively). The EBF prevalences based on 24-h recall at 12 weeks in the intervention and control clusters were 310 (79%) of 392 and 139 (35%) of 402, respectively, in Burkina Faso (prevalence ratio 2·29, 95% CI 1·33-3·92); 323 (82%) of 396 and 161 (44%) of 369, respectively, in Uganda (1·89, 1·70-2·11); and 56 (10%) of 535 and 30 (6%) of 485, respectively, in South Africa (1·72, 1·12-2·63). The EBF prevalences based on 7-day recall in the intervention and control clusters were 300 (77%) and 94 (23%), respectively, in Burkina Faso (3·27, 2·13-5·03); 305 (77%) and 125 (34%), respectively, in Uganda (2·30, 2·00-2·65); and 41 (8%) and 19 (4%), respectively, in South Africa (1·98, 1·30-3·02). At 24 weeks, the prevalences based on 24-h recall were 286 (73%) in the intervention cluster and 88 (22%) in the control cluster in Burkina Faso (3·33, 1·74-6·38); 232 (59%) and 57 (15%), respectively, in Uganda (3·83, 2·97-4·95); and 12 (2%) and two (<1%), respectively, in South Africa (5·70, 1·33-24·26). The prevalences based on 7-day recall were 279 (71%) in the intervention cluster and 38 (9%) in the control cluster in Burkina Faso (7·53, 4·42-12·82); 203 (51%) and 41 (11%), respectively, in Uganda (4·66, 3·35-6·49); and ten (2%) and one (<1%), respectively, in South Africa (9·83, 1·40-69·14). Diarrhoea prevalence at age 12 weeks in the intervention and control clusters was 20 (5%) and 36 (9%), respectively, in Burkina Faso (0·57, 0·27-1·22); 39 (10%) and 32 (9%), respectively, in Uganda (1·13, 0·81-1·59); and 45 (8%) and 33 (7%), respectively, in South Africa (1·16, 0·78-1·75). The prevalence at age 24 weeks in the intervention and control clusters was 26 (7%) and 32 (8%), respectively, in Burkina Faso (0·83, 0·45-1·54); 52 (13%) and 59 (16%), respectively, in Uganda (0·82, 0·58-1·15); and 54 (10%) and 33 (7%), respectively, in South Africa (1·31, 0·89-1·93). INTERPRETATION Low-intensity individual breastfeeding peer counselling is achievable and, although it does not affect the diarrhoea prevalence, can be used to effectively increase EBF prevalence in many sub-Saharan African settings. FUNDING European Union Sixth Framework International Cooperation-Developing Countries, Research Council of Norway, Swedish International Development Cooperation Agency, Norwegian Programme for Development, Research and Education, South African National Research Foundation, and Rockefeller Brothers Foundation.

Arsenic-Associated Oxidative Stress, Inflammation, and Immune Disruption in Human Placenta and Cord Blood

Background Arsenic (As) exposure during pregnancy induces oxidative stress and increases the risk of fetal loss and low birth weight. Objectives In this study we aimed to elucidate the effects of As exposure on immune markers in the placenta and cord blood, and the involvement of oxidative stress. Methods Pregnant women were enrolled around gestational week (GW) 8 in our longitudinal, population-based, mother–child cohort in Matlab, an area in rural Bangladesh with large variations in As concentrations in well water. Women (n = 130) delivering at local clinics were included in the present study. We collected maternal urine twice during pregnancy (GW8 and GW30) for measurements of As, and placenta and cord blood at delivery for assessment of immune and inflammatory markers. Placental markers were measured by immunohistochemistry, and cord blood cytokines by multiplex cytokine assay. Results In multivariable adjusted models, maternal urinary As (U-As) exposure both at GW8 and at GW30 was significantly positively associated with placental markers of 8-oxoguanine (8-oxoG) and interleukin-1β (IL-1β); U-As at GW8, with tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ); and U-As at GW30, with leptin; U-As at GW8 was inversely associated with CD3+ T cells in the placenta. Cord blood cytokines (IL-1β, IL-8, IFNγ, TNFα) showed a U-shaped association with U-As at GW30. Placental 8-oxoG was significantly positively associated with placental proinflammatory cytokines. Multivariable adjusted analyses suggested that enhanced placental cytokine expression (TNFα and IFNγ) was primarily influenced by oxidative stress, whereas leptin expression appeared to be mostly mediated by As, and IL-1β appeared to be influenced by both oxidative stress and As. Conclusion As exposure during pregnancy appeared to enhance placental inflammatory responses (in part by increasing oxidative stress), reduce placental T cells, and alter cord blood cytokines. These findings suggest that effects of As on immune function may contribute to impaired fetal and infant health.

Arsenic in drinking water and adult mortality: a population-based cohort study in rural Bangladesh.

Background: Arsenic is a potent human carcinogen and toxicant. Elevated concentration of arsenic in drinking water is a major public-health problem worldwide. We evaluated risks of adult mortality (due to cancer and cardiovascular and infectious diseases) in relation to arsenic exposure through drinking water. Methods: A cohort analysis was applied to survival data prospectively collected during 1991–2000 in a health and demographic surveillance system in Matlab, Bangladesh, where tubewells were installed beginning in the early 1970s. A total of 115,903 persons aged 15 or more years on 1 January 1991 were available for analysis. In this period, 9015 people died and 22,488 were lost to follow-up. Arsenic exposure data were derived from a survey in 2002–2003 of past and current water use and arsenic concentrations in all tubewells. We estimated risk of excess mortality in relation to arsenic exposure, using proportional hazards models. Results: Even at low levels (10–49 μg/L) of arsenic in drinking water, we observed increased risk of death due to all nonaccidental causes (hazard ratio = 1.16 [95% confidence interval = 1.06–1.26]). Increased risks at exposure of 50–149 μg/L were observed for death due to cancers (1.44 [1.06–1.95]), cardiovascular disease (1.16 [0.96–1.40]), and infectious diseases (1.30 [1.13–1.49]). We observed clear dose-response relationships for each of these causes. Conclusions: Arsenic exposure through drinking water has generated excess adult mortality after 20–30 years of exposure.

Prevalence of arsenic exposure and skin lesions. A population based survey in Matlab, Bangladesh

Study objective: To assess prevalence of arsenic exposure through drinking water and skin lesions, and their variation by geographical area, age, sex, and socioeconomic conditions. Design, setting, and participants: Skin lesion cases were identified by screening the entire population above 4 years of age (n = 166 934) living in Matlab, a rural area in Bangladesh, during January 2002 and August 2003. The process of case identification involved initial skin examinations in the field, followed by verification by physicians in a clinic, and final confirmation by two independent experts reviewing photographs. The tubewell water arsenic concentrations (n = 13 286) were analysed by atomic absorption spectrometry. Drinking water history since 1970 was obtained for each person. Exposure information was constructed using drinking water histories and data on water arsenic concentrations. Main results: The arsenic concentrations ranged from <1 to 3644 μg/l, and more than 70% of functioning tubewells exceeded the World Health Organisation guideline of 10 μg/l. Arsenic exposure had increased steadily from 1970s to the late 1990s, afterwards a decrease could be noted. In total, 504 skin lesions cases were identified, and the overall crude prevalence was 3/1000. Women had significantly higher cumulative exposure to arsenic, while men had significantly higher prevalence of skin lesions (SMR 158, 95% CI 133 to 188). The highest prevalence occurred in 35–44 age groups for both sexes. Arsenic exposure and skin lesions had a positive association with socioeconomic groups and achieved educational level. Conclusions: The result showed sex, age, and socioeconomic differentials in both exposure and skin lesions. Findings clearly showed the urgency of effective arsenic mitigation activities.

Accumulation of cadmium in human placenta interacts with the transport of micronutrients to the fetus.

Cadmium (Cd) is a widespread, highly toxic environmental pollutant known to accumulate in human placenta. The aim of the present study was to elucidate to what extent the accumulation of Cd in human placenta interacts with the transport of micronutrients to the fetus. Cd and micronutrients were measured in placenta and umbilical cord blood from 44 non-smoking, rural Bangladeshi women, using ICPMS. Metallothionein (MT) protein expression was determined in placenta using Western blot. Cd in placenta (median 110 microg/kg dry weight, 20 microg/kg wet weight) was positively associated with maternal urinary Cd. It was also positively associated with Cd in umbilical cord blood (median 0.16 microg/kg), but negatively associated with zinc (Zn; median 3mg/kg) in umbilical cord blood. Umbilical cord blood Zn was positively associated with birth anthropometry measures, and the Cd-related impairment of Zn in umbilical cord blood seemed to decrease size at birth. In multivariate analysis, MT protein expression was associated with Cd (positively) in placenta, but not with Zn or copper (Cu) in placenta. In conclusion, the Cd concentrations in placenta were clearly elevated, which seemed to impair Zn transfer to the fetus. Induction of MT explained the placental accumulation of Cd, but not the impairment of Zn transport.

Arsenic Exposure and Risk of Spontaneous Abortion, Stillbirth, and Infant Mortality

Background: Millions of people worldwide are drinking water with elevated arsenic concentrations. Epidemiologic studies, mainly cross-sectional in design, have suggested that arsenic in drinking water may affect pregnancy outcome and infant health. We assessed the association of arsenic exposure with adverse pregnancy outcomes and infant mortality in a prospective cohort study of pregnant women. Methods: A population-based, prospective cohort study of 2924 pregnant women was carried out during 2002–2004 in Matlab, Bangladesh. Spontaneous abortion was evaluated in relation to urinary arsenic concentrations at gestational week 8. Stillbirth and infant mortality were evaluated in relation to the average of urinary arsenic concentrations measured at gestational weeks 8 and 30. Results: The odds ratio of spontaneous abortion was 1.4 (95% confidence interval [CI] = 0.96–2.2) among women with urine arsenic concentrations in the fifth quintile (249–1253 &mgr;g/L; median = 382 &mgr;g/L), compared with women in the first quintile (<33 &mgr;g/L). There was no clear evidence of increased rates of stillbirth. The rate of infant mortality increased with increasing arsenic exposure: the hazard ratio was 5.0 (95% CI = 1.4–18) in the fifth quintile of maternal urinary arsenic concentrations (268–2019 &mgr;g/L; median = 390 &mgr;g/L), compared with the first quintile (<38 &mgr;g/L). Conclusions: We found evidence of increased risk of infant mortality with increasing arsenic exposure during pregnancy, with less evidence of associations with spontaneous abortion or stillbirth risk.

Arsenic exposure in pregnancy increases the risk of lower respiratory tract infection and diarrhea during infancy in Bangladesh.

Background Previous studies have reported associations between prenatal arsenic exposure and increased risk of infant mortality. An increase in infectious diseases has been proposed as the underlying cause of these associations, but there is no epidemiologic research to support the hypothesis. Objective We evaluated the association between arsenic exposure in pregnancy and morbidity during infancy. Methods This prospective population-based cohort study included 1,552 live-born infants of women enrolled during 2002–2004 in Matlab, Bangladesh. Arsenic exposure was assessed by the concentrations of metabolites of inorganic arsenic in maternal urine samples collected at gestational weeks 8 and 30. Information on symptoms of lower respiratory tract infection (LRTI) and diarrhea in infants was collected by 7-day recalls at monthly home visits. Results In total, 115,850 person-days of observation were contributed by the infants during a 12-month follow-up period. The estimated risk of LRTI and severe LRTI increased by 69% [adjusted relative risk (RR) = 1.69; 95% confidence interval (CI), 1.36–2.09)] and 54% (RR = 1.54; 95% CI, 1.21–1.97), respectively, for infants of mothers with urinary arsenic concentrations in the highest quintile (average of arsenic concentrations measured in early and late gestation, 262–977 μg/L) relative to those with exposure in the lowest quintile (< 39 μg/L). The corresponding figure for diarrhea was 20% (RR = 1.20; 95% CI, 1.01–1.43). Conclusions Arsenic exposure during pregnancy was associated with increased morbidity in infectious diseases during infancy. Taken together with the previous evidence of adverse effects on health, the findings strongly emphasize the need to reduce arsenic exposure via drinking water.

Nutritional Status Has Marginal Influence on the Metabolism of Inorganic Arsenic in Pregnant Bangladeshi Women

Background The interindividual variation in metabolism of inorganic arsenic (iAs), involving methylation via one-carbon metabolism, has been well documented, but the reasons remain unclear. Objectives In this population-based study we aimed to elucidate the effect of nutrition on As methylation among women in Matlab, Bangladesh, where people are chronically exposed to iAs via drinking water. Methods We studied effects of macronutrient status using body mass index (BMI) among 442 women in early pregnancy (gestational week 8), and effects of micronutrient status (plasma folate, vitamin B12, zinc, ferritin, and selenium) among 753 women at gestational week 14. Arsenic metabolites in urine were measured by HPLC combined with hydride generation inductively coupled plasma mass spectrometry. Results The median concentration of As in urine was 97 μg/L (range, 5–1,216 μg/L, adjusted by specific gravity). The average proportions of iAs, monomethylarsonic acid, and dimethylarsinic acid in urine in gestational week 8 were 15%, 11%, and 74%, respectively. Thus, the women had efficient As methylation in spite of being poorly nourished (one-third had BMIs < 18.5 kg/m2) and having elevated As exposure, both of which are known to decrease As methylation. The metabolism of iAs was only marginally influenced by micronutrient status, probably because women, especially in pregnancy and with low folate intake, have an efficient betaine-mediated remethylation of homocysteine, which is essential for an efficient As methylation. Conclusions In spite of the high As exposure and prevalent malnutrition, overall As methylation in women in early pregnancy was remarkably efficient. The As exposure level had the greatest impact on As methylation among the studied factors.

Factors influencing intestinal cadmium uptake in pregnant Bangladeshi women—A prospective cohort study

Experimental studies indicate that zinc (Zn) and calcium (Ca) status, in addition to iron (Fe) status, affect gastrointestinal absorption of cadmium (Cd), an environmental pollutant that is toxic to kidneys, bone and endocrine systems. The aim of this study was to evaluate how various nutritional factors influence the uptake of Cd in women, particularly during pregnancy. The study was carried out in a rural area of Bangladesh, where malnutrition is prevalent and exposure to Cd via food appears elevated. The uptake of Cd was evaluated by associations between erythrocyte Cd concentrations (Ery-Cd), a marker of ongoing Cd exposure, and concentrations of nutritional markers. Blood samples, collected in early pregnancy and 6 months postpartum, were analyzed by inductively coupled plasma mass spectrometry (ICPMS). Ery-Cd varied considerably (range: 0.31-5.4microg/kg) with a median of 1.1microg/kg (approximately 0.5microg/L in whole blood) in early pregnancy. Ery-Cd was associated with erythrocyte manganese (Ery-Mn; positively), plasma ferritin (p-Ft; negatively), and erythrocyte Ca (Ery-Ca; negatively) in decreasing order, indicating common transporters for Cd, Fe and Mn. There was no evidence of Cd uptake via Zn transporters, but the association between Ery-Cd and p-Ft seemed to be dependent on adequate Zn status. On average, Ery-Cd increased significantly by 0.2microg/kg from early pregnancy to 6 months postpartum, apparently due to up-regulated divalent metal transporter 1 (DMT1). In conclusion, intestinal uptake of Cd appears to be influenced either directly or indirectly by several micronutrients, in particular Fe, Mn and Zn. The negative association with Ca may suggest that Cd inhibits the transport of Ca to blood.