Abstract
Background
Arsenic is associated with several adverse health outcomes, including some birth defects. Although diet is the predominant route of arsenic exposure in the United States (U.S.), limited data exist regarding pre-pregnancy dietary arsenic consumption among U.S. women.
Methods
Using data collected in the National Birth Defects Prevention Study (NBDPS), we estimated daily dietary arsenic consumption during the year before pregnancy for 10,886 mothers of nonmalformed control children delivered from 1997–2011. Responses to the NBDPS dietary assessment and food item estimates of total and inorganic arsenic were used to estimate consumption. Associations between total and inorganic arsenic consumption and selected maternal characteristics were estimated using multinomial logistic regression.
Results
Estimates of mean maternal total and inorganic dietary arsenic consumption were 14.9 and 5.2 μg/day, respectively. Several positive and inverse associations with confidence intervals that excluded the null were observed. Comparing mothers in the middle or high total arsenic consumption tertiles to those in the low tertile, we observed positive associations (odds ratios = 1.3–3.8) for maternal age (≥30 years), lower (0–8 years) or higher (>12 years) education, race/ethnicity (non-Hispanic Black, Hispanic, other), and early pregnancy drinking with no binge episodes, and inverse associations (odds ratios = 0.4–0.8) for age (<25 years), body mass index (≥30.0 kg/m2), and early pregnancy smoking. Findings tended to be similar for inorganic arsenic consumption.
Conclusions
These contemporary estimates of pre-pregnancy dietary arsenic consumption among U.S. women show associations between both total and inorganic dietary arsenic consumption and several maternal characteristics, improving characterization of the public health impact of this exposure.
Keywords: arsenic, birth defects, diet, population-based, pregnancy
1 |. INTRODUCTION
Arsenic is a naturally occurring element present in both inorganic and organic species. Inorganic arsenic is recognized as a greater threat to human health than organic arsenic (Hughes, Beck, Chen, Lewis, & Thomas, 2011) as evidenced by reports of positive associations with adverse health outcomes (reviewed in Abdul, Jayasinghe, Chandana, Jayasumana, & De Silva, 2015), including some birth defects (Jin et al., 2016). Most studies examined drinking water exposure. With low arsenic concentrations in finished drinking water throughout much of the United States (U.S.), however, diet is the predominant source of arsenic exposure (Kurzius-Spencer et al., 2014; Xue, Zartarian, Wang, Liu, & Georgopoulos, 2010). Currently, no consensus guidelines exist for tolerable dietary arsenic intake.
Inorganic arsenic contamination is found in rice, grains, vegetables, and fruits (reviewed in Agency for Toxic Substances and Disease Registry, 2007); organic arsenic contamination is found in shellfish (reviewed in Agency for Toxic Substances and Disease Registry, 2007). Contamination varies depending on water and soil composition (Yan-Chu, 1994) and can be affected by previous arsenical pesticide use (reviewed in Agency for Toxic Substances and Disease Registry, 2007). Despite diet being an important route of exposure and associations suggested between arsenic and birth defects, only one study with rather contemporary data (2006–2008) was identified that examined dietary arsenic consumption among U.S. reproductive-aged women. Using total arsenic (all forms) estimates from the U.S. Food and Drug Administration Total Diet Study (TDS) and median food consumption levels for different age–sex groups, investigators estimated dietary arsenic consumption among reproductive-aged women at approximately 0.16 μg/kg-body weight (bw)/day for total arsenic; applying various ratios of organic to inorganic arsenic in foods, estimates of inorganic arsenic consumption ranged from 0.03–0.08 μg/kg-bw/day (Jara & Winter, 2014).
Recently, we analyzed data collected in Iowa for the National Birth Defects Prevention Study (NBDPS) to investigate associations between multisource maternal arsenic exposure, including pre-pregnancy dietary arsenic consumption, and orofacial clefts in offspring (Suhl et al., 2018). We observed values for mothers of nonmalformed controls for total (0.16 μg/kg-bw/day) and inorganic (0.07 μg/kg-bw/day) arsenic similar to those reported previously (Jara & Winter, 2014). The NBDPS is the largest U.S. population-based case-control study of birth defects and enrolled children from 10 sites with estimated dates of delivery (EDDs) from 1997–2011 (Reefhuis et al., 2015). Mothers of control children who participated in the NBDPS were observed to be representative on several characteristics of U.S. mothers who delivered a liveborn child (Cogswell et al., 2009).
Building on our Iowa study, we analyzed data for all NBDPS control mothers to estimate their dietary arsenic consumption during the year before pregnancy and associations with selected characteristics. Our findings provide additional insights into maternal pre-pregnancy dietary arsenic consumption to better characterize the public health impact of this exposure.
2 |. MATERIALS AND METHODS
2.1 |. Study sample
NBDPS methods are detailed elsewhere (Reefhuis et al., 2015). NBDPS control children were a random sample of nonmalformed livebirths selected from hospital delivery logs or birth certificate files and delivered during the same timeframe and geographic catchment areas as case children. We restricted analyses to data reported by NBPDS control mothers as they may be more representative of the underlying distribution of pre-pregnancy dietary arsenic consumption among the general U.S. population than case mothers. The NBDPS protocol was approved by the institutional review board at the Centers for Disease Control and Prevention and each NBDPS site.
2.2 |. Exposure assessment
NBDPS data collection included a telephone interview with case and control mothers administered 6 weeks to 24 months after their EDDs. The interview included a 58-item food frequency questionnaire (FFQ) adapted from the Willett FFQ (Willett, Reynolds, Cottrell-Hoehner, Sampson, & Browne, 1987) to assess diet for the year before pregnancy. Dietary arsenic exposure methods are detailed elsewhere (Suhl et al., 2018). Briefly, each FFQ item was linked to all corresponding items in the TDS 1991–2005 (U.S. Food and Drug Administration, 2007) and 2006–2013 (U.S. Food and Drug Administration, 2017), and mean total arsenic concentrations were estimated for each FFQ item. The TDS assumes estimates below the limit of detection to be 0 μg/g; therefore, all such estimates were assumed to be 0 μg/g in our study. Because the NBDPS collected consumption estimates for the year before pregnancy, to retain the same TDS estimates for mothers with EDDs within the same calendar year, those with EDDs in 2006 were linked to 1991–2005 estimates, and those with EDDs in 2007 were linked to 2006–2013 estimates. For each mother who completed the FFQ, grams consumed of each FFQ item/day was estimated using their reported number of servings consumed/day and the item’s grams/serving, as reported in the U.S. Department of Agriculture Food Composition Database (U.S. Department of Agriculture, 2016). Grams consumed of each FFQ item/day were multiplied by the corresponding TDS mean arsenic concentration estimates to obtain the amount of arsenic consumed per FFQ item/day (μg/day). Total arsenic consumption (μg/day) was estimated by summing across all FFQ items. Inorganic arsenic consumption was estimated using the same approach but applying estimates reported in Schoof et al. (1999). Using maternal reported pre-pregnancy weight, we estimated μg/kg-bw/day for total and inorganic arsenic for comparison with previously reported estimates. Of the 58 FFQ items, TDS estimates for total arsenic were available for 55 items, and inorganic arsenic estimates were available for 24 items.
2.3 |. Statistical analysis
We estimated mean, median, SD, and tertiles of exposure (in μg/day and μg/kg-bw/day) for maternal pre-pregnancy total and inorganic dietary arsenic consumption. Mothers who reported total energy intakes of <500 or >5,000 calories/day were excluded from analyses. Crude odds ratios and 95% confidence intervals were estimated using multinomial logistic regression to identify associations between selected maternal characteristics and total and inorganic dietary arsenic consumption; the lowest tertile of consumption was used as the comparator outcome category. Characteristics examined were maternal age and education at delivery, race/ethnicity, pre-pregnancy body mass index, NBDPS site, and early pregnancy (one month before through the third month of pregnancy) alcohol use and cigarette smoke exposure. We examined dietary arsenic exposure independent of drinking water exposure due to challenges we encountered in linking maternal residence to water arsenic measurements in our Iowa study, the generally low arsenic concentrations in U.S. finished drinking water, and the low proportion (8%) of NBDPS mothers that reported using well water. Analyses were conducted using SAS v. 9.4 (SAS Institute Inc., 2013).
3 |. RESULTS
Overall, 11,829 control mothers participated in the NBDPS with 11,157 providing responses to each FFQ item. Of these 11,157 mothers, 271 consumed <500 or >5,000 calories/day and were excluded from analyses, leaving 10,886 mothers. Using FFQ data reported by these 10,886 mothers, we estimated mean maternal pre-pregnancy total dietary arsenic consumption per day at 14.9 μg/day (SD = 22.4; median = 8.2; range = 0.1–699.4; tertiles: low = <4.5, middle = 4.5–15.4, high = ≥15.4 μg/ day) and inorganic dietary arsenic consumption at 5.2 μg/day (SD = 4.0; median = 4.2; range = 0.1–55.3; tertiles: low = <3.2, middle = 3.2–5.5, high = ≥5.5 μg/ day). The respective estimates for mean total and inorganic dietary arsenic consumption in μg/kg-bw/day were 0.23 and 0.08.
We observed several positive and inverse associations between selected maternal characteristics and total dietary arsenic consumption, for which most confidence intervals excluded the null. Mothers in the middle and high tertiles, compared to those in the low tertile, were more likely to be older (≥30 years), have lower (0–8 years) or higher (>12 years) education, be of non-Hispanic Black, Hispanic, or other race/ethnicity, and drink alcohol with no binge events during early pregnancy (odds ratios = 1.3–3.8); these mothers were less likely to be younger (<25 years), obese (≥30 kg/m2), or exposed to cigarette smoke (active smoking only, active and passive smoking) early in pregnancy (odds ratios = 0.4–0.8) (Table 1). Additionally, mostly positive associations were observed for NBDPS site, using Iowa as the reference. Associations observed for inorganic dietary arsenic consumption were similar in direction as those for total arsenic, except for reduced associations for non-Hispanic Black mothers in the middle and high tertiles and reduced associations for mothers who reported early pregnancy alcohol use (Table 2). Results examining tertiles in μg/kg-bw/day were generally similar in direction to those examining tertiles in μg/day (data not shown).
TABLE 1.
Unadjusted associations between selected characteristics and total dietary arsenic consumption among National Birth Defects Prevention Study control mothers, 1997–2011
| Maternal characteristic | Total arsenic (μg/day) |
|||||||
|---|---|---|---|---|---|---|---|---|
| Low (<4.5) (N = 3,629) |
Medium (4.5–15.4) (N = 3,629) |
High (≥15.4) (N = 3,628) |
Medium versus low |
High versus low |
||||
| N | % | N | % | N | % | OR (95% CI) | OR (95% CI) | |
| Age (years)a | ||||||||
| <20 | 507 | 14.0 | 306 | 8.4 | 222 | 6.1 | 0.6 (0.5, 0.7) | 0.4 (0.4, 0.5) |
| 20–24 | 1,034 | 28.5 | 736 | 20.3 | 646 | 17.8 | 0.7 (0.6, 0.8) | 0.6 (0.6, 0.7) |
| 25–29 | 1,005 | 27.7 | 1,057 | 29.1 | 991 | 27.3 | Referent | Referent |
| 30–34 | 761 | 21.0 | 1,002 | 27.6 | 1,072 | 29.6 | 1.3 (1.1, 1.4) | 1.4 (1.3, 1.6) |
| 35–39 | 261 | 7.2 | 455 | 12.5 | 575 | 15.9 | 1.7 (1.4, 2.0) | 2.2 (1.9, 2.6) |
| ≥40 | 61 | 1.7 | 73 | 2.0 | 122 | 3.4 | 1.1 (0.8, 1.6) | 2.0 (1.5, 2.8) |
| Education (years)a | ||||||||
| 0–8 | 160 | 4.4 | 178 | 4.9 | 200 | 5.6 | 1.4 (1.1, 1.8) | 1.6 (1.3, 2.1) |
| 9–11 | 506 | 14.1 | 360 | 10 | 363 | 10.1 | 0.9 (0.8, 1.1) | 0.9 (0.8, 1.1) |
| 12 | 999 | 27.8 | 773 | 21.5 | 760 | 21.1 | Referent | Referent |
| 13–15 | 983 | 27.3 | 992 | 27.5 | 936 | 26 | 1.3 (1.1, 1.5) | 1.3 (1.1, 1.4) |
| ≥16 | 952 | 26.4 | 1,301 | 36.1 | 1,344 | 37.3 | 1.8 (1.6, 2.0) | 1.9 (1.6, 2.1) |
| Race/ethnicity | ||||||||
| Non-Hispanic White | 2,399 | 66.1 | 2,161 | 59.6 | 1,854 | 51.1 | Referent | Referent |
| Non-Hispanic Black | 201 | 5.5 | 362 | 10.0 | 591 | 16.3 | 2.0 (1.7, 2.4) | 3.8 (3.2, 4.5) |
| Hispanic | 837 | 23.1 | 881 | 24.3 | 895 | 24.7 | 1.2 (1.0, 1.3) | 1.4 (1.2, 1.6) |
| Other | 191 | 5.3 | 224 | 6.2 | 286 | 7.9 | 1.3 (1.1, 1.6) | 1.9 (1.6, 2.4) |
| Pre-pregnancy BMI (kg/m2) | ||||||||
| <18.5 | 202 | 5.8 | 189 | 5.4 | 165 | 4.8 | 0.9 (0.7, 1.1) | 0.8 (0.6, 1.0) |
| 18.5–24.9 | 1,794 | 51.3 | 1,889 | 54.1 | 1,912 | 55.3 | Referent | Referent |
| 25–30.0 | 811 | 23.2 | 784 | 22.4 | 795 | 23.0 | 0.9 (0.8, 1.0) | 0.9 (0.8, 1.0) |
| ≥30.0 | 688 | 19.7 | 633 | 18.1 | 584 | 16.9 | 0.9 (0.8, 1.0) | 0.8 (0.7, 0.9) |
| NBDPS site | ||||||||
| Arkansas | 495 | 13.6 | 507 | 14.0 | 394 | 10.9 | 1.3 (1.1, 1.5) | 1.4 (1.2, 1.7) |
| California | 437 | 12.0 | 384 | 10.6 | 373 | 10.3 | 1.1 (0.9, 1.3) | 1.5 (1.2, 1.8) |
| Georgia | 214 | 5.9 | 347 | 9.6 | 500 | 13.8 | 2.0 (1.6, 2.5) | 4.1 (3.3, 5.1) |
| Iowa | 514 | 14.2 | 418 | 11.5 | 290 | 8.0 | Referent | Referent |
| Massachusetts | 318 | 8.8 | 409 | 11.3 | 553 | 15.2 | 1.6 (1.3, 1.9) | 3.1 (2.5, 3.8) |
| New Jersey | 112 | 3.1 | 165 | 4.6 | 277 | 7.6 | 1.8 (1.4, 2.4) | 4.4 (3.4, 5.7) |
| New York | 314 | 8.7 | 289 | 8.0 | 337 | 9.3 | 1.1 (0.9, 1.4) | 1.9 (1.5, 2.3) |
| North Carolina | 322 | 8.9 | 339 | 9.3 | 280 | 7.7 | 1.3 (1.1, 1.6) | 1.5 (1.2, 1.9) |
| Texas | 421 | 11.6 | 410 | 11.3 | 407 | 11.2 | 1.2 (1.0, 1.4) | 1.7 (1.4, 2.1) |
| Utah | 482 | 13.3 | 361 | 10.0 | 217 | 6.0 | 0.9 (0.8, 1.1) | 0.8 (0.6, 1.0) |
| Alcohol useb,c | ||||||||
| No drinking | 2,357 | 65.8 | 2,188 | 61.1 | 2,234 | 62.1 | Referent | Referent |
| Drinking with no binge episodes | 730 | 20.4 | 951 | 26.7 | 957 | 26.6 | 1.4 (1.3, 1.6) | 1.4 (1.2, 1.5) |
| Drinking and ≥1 binge episode | 496 | 13.8 | 443 | 12.4 | 408 | 11.3 | 1.0 (0.8, 1.1) | 0.9 (0.8, 1.0) |
| Cigarette smoke exposureb | ||||||||
| No active or passive smoking | 2,336 | 64.9 | 2,550 | 71.0 | 2,637 | 73.0 | Referent | Referent |
| Active smoking only | 330 | 258 | 9.2 | 7.2 | 231 | 6.4 | 0.7 (0.6, 0.9) | 0.6 (0.5, 0.7) |
| Passive smoking only | 450 | 445 | 12.5 | 12.4 | 445 | 12.3 | 0.9 (0.8, 1.0) | 0.9 (0.8, 1.0) |
| Active and passive smoking | 484 | 341 | 13.4 | 9.5 | 299 | 8.3 | 0.7 (0.6, 0.8) | 0.6 (0.5, 0.6) |
Abbreviations: BMI, body mass index; CI, confidence interval; NBDPS, National Birth Defects Prevention Study; OR, odds ratio.
At delivery.
During the period one month before conception through the third month of pregnancy.
Binge drinking defined as 4 or more drinks in one sitting.
TABLE 2.
Unadjusted associations between selected characteristics and inorganic dietary arsenic consumption among National Birth Defects Prevention Study control mothers, 1997–2011
| Inorganic arsenic (μg/day) |
||||||||
|---|---|---|---|---|---|---|---|---|
| Low (<3.2) (N = 3,629) |
Medium (3.2–5.5) (N = 3,629) |
High (≥5.5) (N =3,628) |
Medium versus low |
High versus low |
||||
| Maternal characteristic | N | (%) | N | (%) | N | (%) | OR (95% CI) | OR (95% CI) |
| Age (years)a | ||||||||
| <20 | 481 | 13.3 | 254 | 7.0 | 300 | 8.3 | 0.5 (0.4, 0.6) | 0.6 (0.5, 0.7) |
| 20–24 | 930 | 25.6 | 714 | 19.7 | 772 | 21.3 | 0.7 (0.6, 0.8) | 0.8 (0.7, 0.9) |
| 25–29 | 995 | 27.4 | 1,065 | 29.4 | 993 | 27.4 | Referent | Referent |
| 30–34 | 815 | 22.5 | 1,050 | 28.9 | 970 | 26.7 | 1.2 (1.1, 1.4) | 1.2 (1.0, 1.4) |
| 35–39 | 332 | 9.2 | 470 | 13.0 | 489 | 13.5 | 1.3 (1.1, 1.6) | 1.5 (1.3, 1.7) |
| ≥40 | 76 | 2.1 | 76 | 2.1 | 104 | 2.9 | 0.9 (0.7, 1.3) | 1.4 (1.0, 1.9) |
| Education (years)a | ||||||||
| 0–8 | 155 | 4.3 | 179 | 5.0 | 204 | 5.7 | 1.5 (1.2, 2.0) | 1.7 (1.4, 2.2) |
| 9–11 | 467 | 13.0 | 330 | 9.2 | 432 | 12.0 | 0.9 (0.8, 1.1) | 1.2 (1.0, 1.4) |
| 12 | 1,007 | 28 | 754 | 20.9 | 771 | 21.4 | Referent | Referent |
| 13–15 | 1,034 | 28.8 | 994 | 27.6 | 883 | 24.5 | 1.3 (1.1, 1.5) | 1.1 (1.0, 1.3) |
| ≥16 | 934 | 26.0 | 1,346 | 37.4 | 1,317 | 36.5 | 1.9 (1.7, 2.2) | 1.8 (1.6, 2.1) |
| Race/ethnicity | ||||||||
| Non-Hispanic White | 2,304 | 63.5 | 2,333 | 64.3 | 1,777 | 49.0 | Referent | Referent |
| Non-Hispanic Black | 461 | 12.7 | 339 | 9.3 | 354 | 9.8 | 0.7 (0.6, 0.8) | 1.0 (0.9, 1.2) |
| Hispanic | 701 | 19.3 | 794 | 21.9 | 1,118 | 30.8 | 1.1 (1.0, 1.3) | 2.1 (1.8, 2.3) |
| Other | 161 | 4.4 | 163 | 4.5 | 377 | 10.4 | 1.0 (0.8, 1.3) | 3.0 (2.5, 3.7) |
| Pre-pregnancy BMI (kg/m2) | ||||||||
| <18.5 | 193 | 5.5 | 155 | 4.5 | 208 | 6.0 | 0.8 (0.6, 1.0) | 1.0 (0.8, 1.3) |
| 18.5–24.9 | 1,823 | 51.9 | 1,859 | 53.4 | 1,913 | 55.5 | Referent | Referent |
| 25–30.0 | 796 | 22.7 | 841 | 24.2 | 753 | 21.8 | 1.0 (0.9, 1.2) | 0.9 (0.8, 1.0) |
| ≥30.0 | 701 | 20 | 628 | 18 | 576 | 16.7 | 0.9 (0.8, 1.0) | 0.8 (0.7, 0.9) |
| NBDPS site | ||||||||
| Arkansas | 677 | 18.7 | 444 | 12.2 | 275 | 7.6 | 0.8 (0.7, 1.0) | 0.6 (0.5, 0.8) |
| California | 363 | 10.0 | 375 | 10.3 | 456 | 12.6 | 1.3 (1.1, 1.6) | 1.9 (1.6, 2.3) |
| Georgia | 310 | 8.5 | 376 | 10.4 | 375 | 10.3 | 1.5 (1.2, 1.8) | 1.8 (1.5, 2.3) |
| Iowa | 496 | 13.7 | 401 | 11.1 | 325 | 9.0 | Referent | Referent |
| Massachusetts | 274 | 7.6 | 450 | 12.4 | 556 | 15.3 | 2.0 (1.7, 2.5) | 3.1 (2.5, 3.8) |
| New Jersey | 110 | 3.0 | 175 | 4.8 | 269 | 7.4 | 2.0 (1.5, 2.6) | 3.7 (2.9, 4.9) |
| New York | 274 | 7.6 | 322 | 8.9 | 344 | 9.5 | 1.5 (1.2, 1.8) | 1.9 (1.6, 2.4) |
| North Carolina | 361 | 10.0 | 307 | 8.5 | 273 | 7.5 | 1.1 (0.9, 1.3) | 1.2 (0.9, 1.4) |
| Texas | 406 | 11.2 | 396 | 10.9 | 436 | 12.0 | 1.2 (1.0, 1.5) | 1.6 (1.3, 2.0) |
| Utah | 358 | 9.9 | 383 | 10.6 | 319 | 8.8 | 1.3 (1.1, 1.6) | 1.4 (1.1, 1.7) |
| Alcohol useb,c | ||||||||
| No drinking | 2,255 | 63.0 | 2,194 | 61.2 | 2,330 | 64.8 | Referent | Referent |
| Drinking with no binge episodes | 477 | 13.3 | 476 | 13.3 | 394 | 11.0 | 1.0 (0.9, 1.2) | 0.8 (0.7, 0.9) |
| Drinking and ≥1 binge episode | 849 | 23.7 | 915 | 25.5 | 874 | 24.3 | 1.1 (1.0, 1.2) | 1.0 (0.9, 1.1) |
| Cigarette smoke exposureb | ||||||||
| No active or passive smoking | 2,277 | 63.3 | 2,603 | 72.1 | 2,643 | 73.5 | Referent | Referent |
| Active smoking only | 328 | 9.1 | 264 | 7.3 | 227 | 6.3 | 0.7 (0.6, 0.8) | 0.6 (0.5, 0.7) |
| Passive smoking only | 509 | 14.2 | 398 | 11.0 | 433 | 12.0 | 0.7 (0.6, 0.8) | 0.7 (0.6, 0.8) |
| Active and passive smoking | 483 | 13.4 | 346 | 9.6 | 295 | 8.2 | 0.6 (0.5, 0.7) | 0.5 (0.5, 0.6) |
Abbreviations: BMI, body mass index; CI, confidence interval; NBDPS, National Birth Defects Prevention Study; OR, odds ratio.
At delivery.
During the period one month before conception through the third month of pregnancy.
Binge episode defined as 4 or more drinks in one sitting.
4 |. DISCUSSION
Among NBDPS control mothers, we estimated mean pre-pregnancy daily consumption of total and inorganic arsenic at 14.9 μg/day (0.23 μg/kg-bw/day) and 5.2 μg/day (0.08 μg/kg-bw/day), respectively. Our estimates for total and inorganic arsenic were higher than (total) or similar to (inorganic) those reported for U.S. reproductive-aged women reported during a contemporaneous time period (Jara & Winter, 2014). Compared to earlier reported estimates (1981–1996), our estimates were lower for total arsenic (reviewed in Agency for Toxic Substances and Disease Registry, 2007; Gunderson, 1988) but similar for inorganic arsenic (reviewed in Agency for Toxic Substances and Disease Registry, 2007). We identified several positive and inverse associations for selected maternal characteristics when comparing middle and high levels of total and inorganic arsenic consumption to the respective low levels. These novel data can help guide strategies to reduce pre-pregnancy dietary intake of arsenic among U.S. reproductive-aged women.
The previous studies and our current study used total arsenic concentration estimates provided by the TDS. Total arsenic is a composite measure of several arsenic species. Examination of total arsenic may mask the effects of harmful arsenic species, as arsenic metabolism and its associated toxicity varies depending on the species. Inorganic arsenic is metabolized into forms that are considered to be highly toxic (Thomas, Styblo, & Lin, 2001), whereas organic arsenic is excreted virtually unchanged in humans (Taylor et al., 2017). Although some foods (e.g., seafoods) are high in total arsenic, it is primarily organic, which is less harmful than inorganic arsenic (reviewed in Agency for Toxic Substances and Disease Registry, 2007).
Available information on inorganic arsenic in food is sparse, limiting dietary inorganic arsenic consumption estimation. A single study reported inorganic arsenic concentration estimates in food (Schoof et al., 1999); however, foods only were collected from two communities in Texas in 1997. These estimated inorganic arsenic concentrations may not accurately reflect concentrations in foods consumed throughout the U.S. due to the use of global food sources in the U.S. (Pirog, Van Pelt, Enshayan, & Cook, 2001) and the variability in concentrations in water used for cooking, which can influence the inorganic arsenic content in foods (Bae et al., 2002). These limitations underscore the need for improved estimates of inorganic arsenic content in foods.
Our study was strengthened by examining associations between maternal characteristics and pre-pregnancy dietary arsenic consumption among a nationally representative sample of U.S. women who delivered a liveborn child, which were not examined in previous studies, as well the use of individual FFQ reports and inorganic arsenic estimates for individual food items. Conversely, our study may have been limited by reliance on retrospective recall of pre-pregnancy diet; however, dietary recall among pregnant and nonpregnant women is similar (Ramage et al., 2015). Another limitation was that FFQ items for common sources of dietary arsenic, such as shrimp (organic) and rice (inorganic) (reviewed in Agency for Toxic Substances and Disease Registry, 2007), were omitted (shrimp) or grouped with other food items (rice). Also, total or inorganic arsenic estimates were not available for all FFQ items, underestimating dietary arsenic consumption. Additionally, wine may contain inorganic arsenic (Wilson, 2015), but its consumption was not queried separately. Finally, with the present data, it is difficult to meaningfully explore differences observed in arsenic consumption across NBDPS sites.
In summary, we estimated pre-pregnancy dietary arsenic consumption among a more contemporary, nationally representative sample of U.S. women who delivered a liveborn child. Associations between dietary arsenic consumption and several maternal characteristics also were observed. Currently, no consensus guidelines exist for dietary arsenic intake, and the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives recently withdrew their provisional tolerable arsenic intake of 2.1 μg/kg-bw/day, as it was considered not protective of human health (Joint FAO/WHO Expert Committee on Food Additives, 2011). Similarly, the U.S. Environmental Protection Agency reference dose (daily dose likely to be without an appreciable risk of noncancer effects) for inorganic arsenic is 0.3 μg/kg-bw/day (reviewed in Agency for Toxic Substances and Disease Registry, 2007); however, this estimate was based on dermal and cardiovascular effects. As such, it is difficult to meaningfully interpret how reported levels of pre-pregnancy dietary arsenic consumption impact pregnancy outcomes. Additional research is needed to improve estimates of inorganic arsenic content in foods and better characterize arsenic consumption among this population, as well as its contribution to the development of birth defects.
ACKNOWLEDGMENTS
We thank the study participants and study staff who contributed to the National Birth Defects Prevention Study (NBDPS). We also thank Dr. Anna Maria Siega-Riz for her review and expert comments on the manuscript. This work was funded by the Centers for Disease Control and Prevention cooperative agreements under PA #96043, PA #02081, FOA #DD09-001, FOA #DD13-003, and NOFO #DD18-001 to the Centers for Birth Defects Research and Prevention participating in the NBDPS and/or the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS), and grants (U01 DD001035 and U01 DD001223) awarded to the Iowa Center for Birth Defects Research and Prevention. The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Funding information
Centers for Disease Control and Prevention, Grant/Award Numbers: U01 DD001035, U01 DD001223
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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