TABLE 15
Key epidemiological studies relating As exposure with birth weight.
| Reference study population design | Outcome definition | Population size (n) | Arsenic exposure a | Results | Additional information/confounders |
|---|---|---|---|---|---|
| Included in 2009 EFSA Opinion | |||||
|
Hopenhayn et al. (2003) Chile Cohort | BW | 844 (442 from Antofagasta and 444 from Valparaiso) | Water: Antofagasta: 30–40 μg/L Valparaiso: < 1 μg/L | −57 g in Antofagasta (95% CI ‐123, +9) |
Aggregated w‐As data Adjusted for many potential confounders, including GA |
|
Yang et al. (2003) Taiwan Cohort | BW | 18,259 (3872 from As‐exposed townships, and 14,387 from similar reference townships) | Water: In As‐exposed townships 30% > 50 μg/L | −29 g (95% CI –44, –14) in As‐exposed townships | Aggregated w‐As data. Adjusted for some potential confounders |
|
Huyck et al. (2007) Rural Dacca, Bangladesh CS/cohort (samplings early pregnancy and around birth) | BW, LBW | 49 live births |
Water: max Q1: 0.5, Q2: 1.3, Q3: 9.0, Q4: 734 μg/L. Maternal hair 0.14–3.3, toenail 0.2–6.2 (both t‐As μg/g) |
−194 g per μg/g As in hair No association between BW and water‐As or nail‐As OR for LBW versus hair As around 2 but CI included 1 |
LBW = < 2750 (=median in these newborns). Poor correlations between w‐As and most biomarkers Adjusted for a number of potential confounders including GA |
|
Rahman et al. (2009) Matlab Bangladesh Cohort | BW | 1578 singleton live births | Maternal u‐tiAs: median 95 μg/L |
No overall association, but −1.7 g per μg/L in u‐tiAs at 0–100 μg/L. Mean BW 2.6 kg | Adjusted for many potential confounders. Exposure from water (70% > 10 μg/L, see Rahman et al., 2006) |
|
Myers et al. (2010) Inner Mongolia, China CS | BW in term births | 9890 singleton births 1996–1999 with As measured in the wells of the sub village | Water: 66% < 20, 20% 21–50, 7% 50–100, 7% > 100 μg/L. Data from 1991 to 1997 in well‐water registry | No association between BW and water‐As categories | w‐As data were averaged by sub village. No potential confounders were detected for BW. Women were generally health and well‐nourished |
| Not included in the 2009 Opinion | |||||
|
Kwok et al. (2006) Rural Bangladesh, 261 villages in 3 districts CS | LBW in term (≥ 37 week) births | 2006 live singleton births with As measured in the wells of the villages | Water: 2003 samples, mean about 70 μg/L, six categories < 10 μg/L to > 300 μg/L |
Adjusted OR 1.00 for LBW (< 2500 g) in full term births BW not analysed as continuous variable | Water samples (for each household), birth data for 2002, and covariates were collected in 2003 from Community Centres' registers + maternal interviews (2003). Most births at home |
|
Gelmann et al. (2013) Romania CS | LBW | 38 singleton live births with LBW and normal BW from As‐in‐water exposed (19) and unexposed (19) villages | Water: means in exposed 54 μg/L and in unexposed 1 μg/L. u‐iAs 2–90 μg/L in exp and 0–1 μg/L in unexposed | Among exposed those with LBW had higher u‐tiAs than those with normal BW | Pilot study with too few cases |
|
Chou et al. (2014) Taiwan Cohort | BW, LBW | 299 live births, 21 (7%) LBW (< 2500 g) | Maternal u‐tiAs. Median 22 μg/g Cr (90% DMA) | Significant adjusted association (multiple linear regression) between u‐MMA and BW. No association with LBW | The association btw u‐MMA and BW disappeared after further adjustment for DNA damage (N7‐MeG) |
|
Laine et al. (2015) Mexico CS | BW | 199 singleton live births, only 4 with LBW | Water: < 0.5–236, median 13 μg/L. Maternal u‐tiAs median 23 μg/L |
w‐As, u‐tiAs, u‐DMA: null U‐MMA and U‐%MMA had a significant adjusted negative slope | Mean u‐DMA 43 μg/L in women reporting seafood and 31 μg/L in the others. The association with BW seemed to be at least partly caused by an association with GA |
|
Bloom et al. (2016) Romania CS | BW | 122 live singleton births | Water: mean 4.1 μg/L | No overall association between As and BW | Adjusted for potential confounders. An inverse association was found in the 29 smoking mothers |
|
Gilbert‐Diamond et al. (2016) USA, New Hampshire Cohort | BW | 706 live singleton births | Maternal u‐tiAs. Median 3.4 μg/L | No association between u‐tiAs, MMA or DMA and BW | General additive models adjusted for some potential confounders including gestational age |
|
Kile, Cardenas, et al. (2016) Rural Bangladesh Cohort | BW | 1153 live singleton births |
Water: < 0.5–1400, median 2.3 μg/L Maternal toenail t‐As 0.2–35 μg/g, median 1.5 μg/g | Significant adjusted inverse association (multiple linear regression) between water As and BW, and between nail‐As and BW | Structural equation modelling suggested that almost all the association was mediated by an association with GA |
|
Almberg et al. (2017) USA, Ohio CS | LBW and VLBW (< 1500 g) in term infants | 428,804 live singleton births from records 2006–2008. In term births 2.9% LBW and 1.2% VLBW | W‐As aggregated by 88 counties and year: 0.5–12 μg/L, median 1.5 μg/L. Based on 2968 measurements in 975 water systems | Adjusted ORs for LBW (1.00) and VLBW (0.99) were normal |
ORs adjusted for many potential confounders from the records ORs were increased in some sub analyses excluding counties with many private wells |
|
Rahman et al. (2017) Rural Bangladesh Cohort | BW | 1180 live singleton births, same study base as Kile, Cardenas, et al. (2016) | See Kile, Cardenas, et al. (2016), but median w‐As here 2.2 μg/L and nail‐As 1.2 μg/g | Associations: See Kile, Cardenas, et al. (2016) | Mediation analyses suggested that most of the association was mediated by GA, but among the smallest infants there was also a direct effect |
|
Lin et al. (2019) Rural Bangladesh Cohort | BW | 1057 live singleton births, Same study bas as Kile, Cardenas, et al. (2016) and Rahman et al. (2017) | Toenail As 0.04–47, median 1.2 | BW inversely associated with protein, fat and fibre intake, but positively associated with carbohydrate intake. Nail‐As not significantly associated with BW, when adjusted for macronutrients, and nail‐As was not a significant mediator for BW | Seems to weaken the conclusions from Kile, Cardenas, et al. (2016) regarding BW versus nail‐As, where macronutrients were not adjusted for. But still association between nail‐As and GA; the latter was a mediator to BW in Kile, Cardenas, et al. (2016) |
|
Bozack et al. (2020) Rural Bangladesh Cohort | BW | Subset of Kile, Cardenas, et al. (2016): 413 births with % methylation of DNA cord blood at 3 CpG sites in the gene body of DNA methyltransferase 3 alpha | See Kile, Cardenas, et al. (2016) | Significant inverse association between nail‐As and BW. | See Kile, Cardenas, et al. (2016), Rahman et al. (2017) and Lin et al. (2019). Here structural equation modelling also includes DNA methylation in cord blood. |
|
Howe, Farzan, et al. (2020) USA, Los Angeles Cohort | BW |
Births with maternal: 116 (hair‐As) 100 (blood As) 167 (u‐iAs) |
Medians: Hair: 0.01 μg/g Blood: 0.67 μg/g u‐tiAs: 5.7 μg/L | No association with u‐tiAs | In urine additionally 0.5 μg/L AsB |
| Howe, Claus Henn, et al. (2020) | BW | 262 | Median u‐tiAs 5.8 μg/L | No significant association with BW in relation to GA | Note that then a possible impact of As on BW via GA is not taken into account |
|
Shih et al. (2020) USA, seven areas Cohort (NCS) | BW | 212 | Total As (median 7.8 and DMA median 3.4 μg/L) in maternal urine | No association btw u‐DMA and BW | High LODs: u‐tiAs 1.25, DMA 1.7, MMA 0.9. All had u‐tiAs >LOD and 77% had DMA > LOD, but for other species > 60% < LOD |
|
Bulka et al. (2022) USA nationwide Cross‐sectional | BW | 3,305,090 term births in 3105 counties | The probability of As in water in four categories (≤ 1, > 1, ≤ 5, > 5, ≤ 10, > 10) was estimated in 1 × 1 km grids, based on about 20,000 As measurements in private wells. Estimates were then aggregated on county level |
Adjusted beta (grams) per 10% increase in probability of exceeding the following thresholds: ≤ 1, > 1 −3.1 (−4.0, −2.2) ≤ 5, > 5 −2.8 (−4.2, −1.3) ≤ 10, > 10 −3.9 (−6.1, −1.7) | Adjusted for proportion of private wells, maternal age, race/ethnicity, marital status, education, smoking during pregnancy, pre‐pregnancy BMI, rurality/urbanicity, annual concentration of PM < 2.5 μm in the county |
Abbreviations: As, arsenic; AsB, arsenobetaine; BMI, body mass index; BW, birth weight; CI, confidence interval; Cr, creatinine; CpG, cytosine‐phosphate‐guanine; CS, cross‐sectional study; DMA, sum of dimethylarsinous acid and dimethylarsinic acid; DNA, deoxyribonucleic acid; EFSA, European Food Safety Authority; GA, gestational age; iAs, inorganic arsenic; km, kilometre(s); LBW, low birth weight; LOD, limit of detection; MMA, sum of monomethylarsonous acid and monomethylarsonic acid; n, number; N7‐MeG, N7‐methylguanine; NCS, National Children's Study; OR, odds ratio; PM, particulate matter; t‐As, total arsenic; u‐DMA, urinary DMA; u‐iAs, urinary inorganic arsenic; u‐MMA, urinary MMA; USA, United States of America; u‐tiAs, total urinary iAs (sum of iAs and methylated its metabolites MMA and DMA); VLBW, very low birth weight; w‐As, water arsenic.