TABLE 16.
Key epidemiological studies on associations between As exposure and preterm birth (PTB GA < 37 weeks) or gestational age (GA).
| Reference study population design | Outcome definition | Population size (n) | Arsenic exposure a | Results | Additional information/confounders |
|---|---|---|---|---|---|
|
Yang et al. (2003) Taiwan Cohort |
PTB | 18,259 (3872 from As‐exposed townships, and 14,387 from similar reference townships) | Water: In As‐exposed townships 30% > 50 μg/L | 639 cases (3.5%) of PTB. OR 1.10 (0.91–1.33) for As‐exposed women | Aggregated water As data. Adjusted for some potential confounders |
|
Myers et al. (2010) Inner Mongolia, China CS |
PTB | 9890 singleton births 1996–1999 with As measured in the wells of the subvillage | Water: 66% < 20, 20% 21–50, 7% 50–100, 7% > 100 μg/L. Data from 1991 to 1997 in well‐water registry | 289 cases (2.9%) of PTB. OR 1.02 (0.72–1.44) for water‐As > 50 versus < 50 μg/L | Water‐As data were averaged by subvillage. Adjusted only for antenatal care. No other potential confounders were detected. Women were generally health and well‐nourished |
|
Laine et al. (2015) Mexico CS |
GA | 199 singleton live births, only 3 with PTB | Water: < 0.5–236, median 13 μg/L. Maternal u‐tiAs median 23 μg/L |
Median GA 39 weeks No association btw w‐As, u‐DMA and GA u‐tiAs, u‐MMA and u‐%MMA had significant adjusted negative slopes |
Mean u‐DMA 43 μg/L in women reporting seafood and 31 μg/L in the others |
|
Gilbert‐Diamond et al. (2016) USA, New Hampshire Cohort |
GA | 706 live singleton births | Maternal u‐tiAs. Median 3.4 μg/L | Median GA 39.5. No association btw u‐tiAs, MMA or DMA and GA | General additive models adjusted for some potential confounders |
|
Kile, Cardenas, et al. (2016) Rural Bangladesh Cohort |
GA | 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 |
254 (22%) with PTB. Significant adjusted inverse association (multiple linear regression) btw water As and GA, and btw nail‐As and GA | Structural equation modelling suggested that the impact of As on GA mediated almost all the association btw As and birth weight |
|
Almberg et al. (2017) USA, Ohio CS |
PTB | 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 (only regulated water systems, As in private wells unknown) |
11% were PTB. Overall adjusted OR (per mean As in μg/L) for PTB 0.99 (0.98–1.01). Adjusted OR for women from counties with < 20% private wells: 1.08 (1.02–1.14) |
ORs adjusted for many potential confounders from the records. ORs were increased in subanalyses excluding counties with many private wells |
|
Lin et al. (2019) Rural Bangladesh Cohort |
GA | 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 μg/g | GA inversely associated with protein, fat and fibre intake, but positively associated with carbohydrate intake. Nail As inversely associated with GA, when adjusted for macronutrients | As Kile, Cardenas, et al. (2016), but points out the impact of macronutrients, some of which are also associated with As |
|
Bozack et al. (2020) Rural Bangladesh Cohort |
GA | Subset of Kile, Cardenas, et al. (2016): 413 births with % methylation of DNA cord blood at 3 CpG sites in the DNA sequence of the gene DNA methyltransferase 3 alpha | See Kile, Cardenas, et al. (2016) | Significant inverse association between nail As and GA | 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 |
GA |
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‐iAs | In urine additionally 0.5 μg/L AsB |
|
Shih et al. (2020) USA, seven areas Cohort (NCS) |
GA | 212 | Total As (median 7.8 and DMA median 3.4 μg/L) in maternal urine | Mean GA 38.8 weeks. No association btw u‐DMA and GA | High LODs: t‐As 1.25, DMA 1.7, MMA 0.9. All had t‐As > LOD and 77% had DMA > LOD, but for other species > 60% < LOD |
|
Bulka et al. (2022) USA nationwide Cross‐sectional |
GA, PTB | 3,580,755 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 −0.01 (−0.01, −0.01) ≤ 5, > 5 −0.01 (−0.01, −0.00) ≤ 10, > 10 −0.00 (−0.02, −0.00) Risk differences for PTB zero in all comparisons |
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; CpG, cytosine‐phosphate‐guanine; CS, cross‐sectional study; DMA, sum of dimethylarsinous acid and dimethylarsinic acid; DNA, deoxyribonucleic acid; GA, gestational age; km, kilometre(s); LOD, limit of detection; LBW, low birth weight; MMA, sum of monomethylarsonous acid and monomethylarsonic acid; n, number; NCS, National Children's Study; OR, odds ratio; PM, particulate matter; PTB, pre‐term birth; t‐As, total arsenic; u‐DMA, urinary DMA; u‐MMA, urinary MMA. u‐tiAs, total urinary inorganic arsenic (sum of inorganic arsenic and its methylated metabolites MMA and DMA); USA, United States of America; VLBW, very low birth weight; w‐As, water‐arsenic.
iAs in urine includes MMA and DMA, but not AsB.