ABSTRACT
Background
Inadequate or excessive intake of micronutrients in pregnancy has potential to negatively impact maternal/offspring health outcomes.
Objective
The aim was to compare risks of inadequate or excessive micronutrient intake in diverse females with singleton pregnancies by strata of maternal age, race/ethnicity, education, and prepregnancy BMI.
Methods
Fifteen observational cohorts in the US Environmental influences on Child Health Outcomes (ECHO) Consortium assessed participant dietary intake with 24-h dietary recalls (n = 1910) or food-frequency questionnaires (n = 7891) from 1999–2019. We compared the distributions of usual intake of 19 micronutrients from food alone (15 cohorts; n = 9801) and food plus dietary supplements (10 cohorts with supplement data; n = 7082) to estimate the proportion with usual daily intakes below their age-specific daily Estimated Average Requirement (EAR), above their Adequate Intake (AI), and above their Tolerable Upper Intake Level (UL), overall and within sociodemographic and anthropometric subgroups.
Results
Risk of inadequate intake from food alone ranged from 0% to 87%, depending on the micronutrient and assessment methodology. When dietary supplements were included, some women were below the EAR for vitamin D (20–38%), vitamin E (17–22%), and magnesium (39–41%); some women were above the AI for vitamin K (63–75%), choline (7%), and potassium (37–53%); and some were above the UL for folic acid (32–51%), iron (39–40%), and zinc (19–20%). Highest risks for inadequate intakes were observed among participants with age 14–18 y (6 nutrients), non-White race or Hispanic ethnicity (10 nutrients), less than a high school education (9 nutrients), or obesity (9 nutrients).
Conclusions
Improved diet quality is needed for most pregnant females. Even with dietary supplement use, >20% of participants were at risk of inadequate intake of ≥1 micronutrients, especially in some population subgroups. Pregnancy may be a window of opportunity to address disparities in micronutrient intake that could contribute to intergenerational health inequalities.
Keywords: pregnancy, micronutrients, diet, dietary supplements, vitamins, minerals, Dietary Reference Intakes
Introduction
Prenatal nutrition has immediate and long-term implications for offspring health (1). Prenatal deficiencies have been associated with offspring neural tube defects (folic acid) (2), alterations in cardiovascular structure (vitamin A) (3), and impaired neurocognitive development (iron, zinc, choline) (4, 5), whereas excessive intake of certain micronutrients, such as the methyl donors folate and vitamin B-12, may increase chronic disease risk in offspring through alterations in DNA methylation (6). Micronutrients may also modify the effect of adverse environmental exposures during pregnancy (7, 8), highlighting the importance of optimizing micronutrient intake in pregnancy for offspring health outcomes.
While micronutrient deficiency is generally a concern in lower-income countries, a 2013 meta-analysis of food intake only reported that many pregnant women in high-income countries also have inadequate micronutrient intake, particularly for folate, vitamin D, and iron (9). More recently, a nationally representative sample of the US pregnant women populations estimated that at least 1 in 3 pregnant women aged 20–40 y were at risk of inadequate intake of vitamin D, vitamin E, and magnesium, while 1 in 10 were at risk of inadequate intake of vitamin A, vitamin B-6, vitamin C, calcium, and zinc, even with dietary supplement use (10). Risk of excessive intake was also notable, with nearly one-third of pregnant women exceeding the Tolerable Upper Intake Level (UL) for folate and iron, and mean intakes of vitamins B-6 and B-12 at 5–10 times the Estimated Average Requirement (EAR) (10). Disparities in risks of inadequate or excessive intake according to race/ethnicity or educational attainment have been reported in a small study (11), suggesting that strategies to optimize micronutrient intake may need to be tailored to specific groups. However, data from large, diverse populations are needed to identify the specific subgroups at risk of inadequate and excessive micronutrient intake in advance of developing targeted approaches to optimize intake.
Here, we explored disparities in risks of inadequate or excessive prenatal micronutrient intakes in a large, diverse sample of pregnant women participating in a national consortium of pregnancy and pediatric cohorts. We compared their intake to the DRIs defined by the Food and Nutrition Board of the Institute of Medicine, which reflect the amount that should be consumed daily to meet the physiological requirements for each sex and life stage that promote health and avoid disease (12). We report risks of inadequate or excessive intake relative to pregnancy-specific DRIs, overall and within maternal age, race/ethnicity, education, and prepregnancy BMI categories. Our goal was to identify patterns of prenatal micronutrient intake that may be contributing to disparities in maternal/child health outcomes (13–16).
Methods
The Environmental influences on Child Health Outcomes (ECHO) is a national consortium of pediatric, longitudinal, observational cohorts established in 2016 by the NIH to understand the effects of early-life exposures on child health and development. Data-collection methods are summarized in Table 1 for the 15 cohorts across 14 states that contributed data from 9801 singleton pregnancies to this analysis. Fourteen cohorts enrolled pregnant females and collected data in pregnancy (n = 9293), and 1 cohort enrolled mothers of children aged 2–5 y, with retrospective assessment of early pregnancy characteristics and dietary intake (n = 508). All cohorts collected sociodemographic and weight-related data via self-report and/or medical records, including age (14–18, 19–30, 31–50 y), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic any race, non-Hispanic other race), education (<high school degree, high school degree, some college or 2-y degree, ≥4-year degree), and prepregnancy BMI (in kg/m2; underweight, <18.5; normal weight, 18.5–24.9; overweight, 25–29.9; obese, ≥30). All cohort-specific protocols were approved by the institutional review boards with jurisdiction in each study location, and all participants provided informed consent. De-identified, individual-level datasets of diet and characteristics were transferred to the University of Colorado under data use agreements.
TABLE 1.
Cohort name, recruitment area (years of data collection) | Specific method or questionnaire (reference) | Gestational range of administration (time frame of recall) | Nutrient database | Supplement database (if applicable) | n |
---|---|---|---|---|---|
24-Hour recalls | |||||
Safe Passage, Sioux Falls and Rapid City, SD (2007–2015) | Interviewer-administered USDA Automated Multiple Pass Method, with supplement module (17) | 20–40 wk gestation (prior 24 h) | University of Minnesota's Nutrition Data System for Research | University of Minnesota's Nutrition Data System for Research | 64 |
Healthy Start, Aurora, CO (2009–2014) | Automated Self-Administered 24-h recall (18) and supplement form querying brand, type, dose | 6–40 wk gestation (prior 24 h) | Food and Nutrient Database for Dietary Studies | Product labels, Dietary Supplement Label Database | 1363 |
ARCH, Lansing, Michigan (2015–2017) | Unstructured 24-h recall | 15–35 wk gestation (prior 24 h) | Food and Nutrient Database for Dietary Studies | — | 50 |
MADRES, Los Angeles, CA(2015–2019) | Automated Self-Administered 24-h recall (18) | 28–38 wk gestation (prior 24 h) | Food and Nutrient Database for Dietary Studies | — | 178 |
Rochester, Rochester, NY (2015–2019) | Interviewer-administered USDA Automated Multiple Pass Method (17) | 16–39 wk gestation (prior 24 h) | University of Minnesota's Nutrition Data System for Research | — | 255 |
Food-frequency questionnaires | |||||
Project Viva,2 Boston, MA(1999–2003) | Self-administered Harvard FFQ (modified for use in pregnancy) (19) and supplement form querying brand, type, dose | 5–40 wk gestation (prior 3 mo) | Harvard nutrient composition database | Harvard nutrient composition database | 1872 |
CHARGE, Davis/Sacramento, CA, and surrounding area (2003–2009) | Self-administered Modified Block-Muldoon FFQ for Pregnancy (with added questions for fish intake/omega-3 fatty acids) (20) and supplement form querying brand, type, dose | Offspring age 2–5 y (reflecting entire prenatal period) | Nutrition Quest nutrient composition database | Product labels, University of Minnesota's Nutrition Data System for Research | 508 |
CANDLE, Shelby County, TN(2006–2011) | Block FFQ 2005 with supplement questions (21) | 15–35 wk gestation (prior 3 mo) | Nutrition Quest nutrient composition database | Nutrition Quest nutrient composition database | 1322 |
MARBLES,2 Davis/Sacramento, CA,and surrounding area (2006–2020) | Block FFQ 2005 (21) with supplement form querying brand, type, dose | 10–40 wk gestation (1–20 wk and 20–40 wk gestation) | Nutrition Quest nutrient composition database | Product labels, University of Minnesota's Nutrition Data System for Research | 221 |
New Hampshire Birth Cohort Study,State of New Hampshire(2009–2018) | Harvard FFQ (22) | 20–40 wk gestation (since becoming pregnant) | Harvard nutrient composition database | — | 1322 |
EARLI,2 Philadelphia, PA; Baltimore,MD; San Francisco Bay Area, CA;Sacramento, CA (2011–2017) | Modified National Cancer Institute Dietary History Questionnaire (23) with supplement form querying brand, type, dose | 16–39 wk gestation (prior 3 mo) | National Cancer Institute's Diet History Questionnaire nutrient database | Product labels, University of Minnesota's Nutrition Data System for Research | 195 |
PRISM, Boston, MA, and New YorkCity, NY (2011–2017) | Interviewer-administered modified Block-Bodnar FFQ with supplement questions (24) | 8–40 wk gestation (prior 3 mo) | Nutrition Quest nutrient composition database | Product labels, Dietary Supplement Label Database, Dietary Supplement Ingredient Database | 567 |
PETALS, Greater San Francisco BayArea, CA (2013–2018) | Self-administered Block FFQ (21) | 10–13 wk gestation (prior 3 mo) | Food and Nutrient Database for Dietary Studies | — | 914 |
Atlanta ECHO Cohort of EmoryUniversity, Atlanta, GA (2014–2019) | Block-Bodnar FFQ with supplement questions (24) | 8–14 and 24–30 wk gestation2 (prior 4 mo) | Food and Nutrient Database for Dietary Studies | Nutrition Quest nutrient composition database | 310 |
NYU CHES, New York City, NY(2016–2019) | National Cancer Institute Dietary History Questionnaire-2 with supplement questions (25) | 18–40 wk gestation (prior 12 mo) | National Cancer Institute's Diet History Questionnaire nutrient database | National Cancer Institute's Diet History Questionnaire nutrient database | 660 |
ARCH, Archive for Resarch in Child Health; CANDLE, Conditions Affecting Neurocognitive Development and Early Learning; CHARGE, CHildhood Autism Risk from Genetics and the Environment Study; EARLI, Early Autism Risk Longitudinal Investigation; ECHO, Environmental influences on Child Health Outcomes; FFQ, food-frequency questionnaire; MADRES, Maternal And Developmental Risks from Environmental and Social Stressors; MARBLES, Markers of Autism Risk in Babies: Learning Early Signs; MARCH, Michigan Archive for Resarch in CHild Health; NYU CHES, New York University Children's Health and Environment Study; PETALS, Pregnancy Environment and Lifestyle Study; PRISM, Pediatric Research using Integrated Sensor Monitoring Systems.
Two or more FFQs were administered during pregnancy and were averaged for analysis.
Dietary data
Five cohorts assessed dietary intake with interviewer- or self-administered 24-h recalls (n = 1910 participants) (17, 18). Two of these cohorts (n = 1427 participants) also assessed dietary supplement use by querying brand name, type, and dose and used to obtain exact estimates of micronutrient content from nutrient databases and/or manufacturer labels. Ten cohorts assessed dietary intake with various food-frequency questionnaires (FFQs; n = 7891 participants) (19–25), including the cohort that retrospectively assessed prenatal diet at offspring age 2–5 y (n = 508). Of these, 8 assessed dietary supplement use (n = 5655 participants), with 4 querying brand name, type, and dose to obtain exact contents. The other 4 cohorts used the supplement questions built into the Block or National Cancer Institute FFQs, which queried type of supplement (prenatal, multivitamin, other single nutrients) and applied mean values of nutrient contents to intake estimates. All cohorts processed their raw dietary data locally using appropriate databases for food and dietary supplement nutritional content at the time of data collection (Table 1). Separately for food and supplements, they provided data on daily intake of 19 micronutrients for which pregnancy-specific DRIs for daily intake exist (12): vitamins A, C, D, E, and K; thiamin; riboflavin; niacin; folate/folic acid; vitamin B-12; choline; calcium; copper; iron; magnesium; phosphorus; zinc; and potassium. We did not analyze selenium because the exact content in food is largely influenced by regional differences in soil composition (26).
Dietary Reference Intakes
We aimed to understand risk of inadequate and excessive intakes by comparing usual daily intakes to the EAR, Adequate Intake (AI), and UL specified by the DRIs (12). The EAR reflects the average daily nutrient intake level estimated to meet the requirements of half of the healthy individuals in a group, such that the prevalence of intakes below the EAR reflects the prevalence of inadequacy. For nutrients without an EAR (vitamin K, choline, potassium), an AI level is provided. The AI is believed to cover the needs of all healthy individuals, such that when the mean intake of a group is at or above the AI, a low prevalence of inadequacy is assumed. The UL is the highest daily nutrient intake likely to pose no risk of adverse health effects to most individuals. While exact nutrient requirements for any specific individual cannot be defined, risk of inadequacy for a population can be estimated with the cut-point method, wherein the prevalence of intakes below the EAR reflects the percentage of the population at risk of inadequate intake (27). For nutrients with an AI, we used the cut-point method to determine the percentage of the population above the AI, for whom risk of inadequacy is assumed to be low. Similarly, the percentage of the population above the UL reflects the proportion at risk of excessive intake. We note that the cut-point method assumes that nutrient requirements are normally distributed within a population, which is not the case for menstruating females whose iron requirement varies according to blood loss during menses (28, 29). However, we elected to use the cut-point method for iron given that all participants were pregnant and not menstruating. For age-stratified analyses, we used the DRIs specified for each age category (14–18, 19–30, 31–50 y) (12). For analyses stratified by the other characteristics (race/ethnicity, education, prepregnancy BMI), we used the DRIs for pregnant females aged 19–30 years because 1) only 4% of participants were 14–18 y and 2) DRIs for pregnant females aged 31–50 y were the same for all nutrients except for magnesium (EAR = 290 vs. 300 mg, respectively).
Estimating usual intake distributions
24-Hour recall data
Cohorts that assessed intake with 24-h recalls provided micronutrient data for ≥1 repeated observation(s) (days) for each participant (70% of participants had ≥2 recalls). We used an extension of the National Cancer Institute's measurement error model to estimate the distribution of usual intakes of micronutrients from food alone for intake assessed with recalls (30). This model produces population point estimates by partitioning out the intraindividual (day-to-day) component of variation when estimating the distributions of intakes. First, we transformed the distributions with the Box-Cox parameter that optimized the normality of the residuals on a per-micronutrient basis. The resulting transformed data produced errors with a distribution more closely approximating normality. We fit a general linear mixed model to the transformed data, extending the measurement error model method as described by Tooze and colleagues (31) to include 2 random effects and thereby account for the 2-level nested clustering. The first random effect accounted for correlation of the repeated recalls within participants. The second random effect accounted for the clustering of participants within ECHO cohorts. The overall variance pattern was thus Kronecker product compound symmetric. The repeated recalls within each participant were assumed to have equal correlation and equal variance. Participants were assumed to be exchangeable within cohort, and thus have equal variance and equal correlation within cohorts. We used the model-provided estimates of the quantiles of the distribution of usual daily intake to calculate the proportion of participants with intakes below the EAR, above the AI, and above the UL.
We also estimated the usual daily intake of micronutrients from food and dietary supplements combined. One cohort with both food and supplement data assessed dietary supplement use as part of the recall but calculated micronutrient intake from each source separately. To estimate usual intake from both sources, we summed the daily intakes from food and supplements. The second cohort with food and supplement data assessed dietary supplement use outside of the recalls with a separate questionnaire up to 3 times in pregnancy. To estimate usual daily intake from both sources in this cohort, we matched recalls with the appropriate questionnaire based on date of administration. Participants who reported daily dietary supplement use at the time of the recall were assumed to have taken the supplement on the day of the recall; thus, we added the dietary supplement intake to the recall (food-based) intake. For participants who reported less than daily dietary supplement use at the time of the recall, we computed the probability that they took the supplement on the day of the recall based on their reported frequency of use (e.g., every other day). We used a Bernoulli distribution (32) to simulate the occurrence of intake on each recall day. If we sampled a success (i.e., result indicating the supplement was taken on the day of the recall), we added the dietary supplement intake to the recall (food-based) intake; otherwise, the dietary supplement intake was not added. We then applied the measurement error model described above to recall data from both cohorts, again obtaining estimates of inadequate or excessive intake from food and supplements, both overall and stratified by sociodemographic and weight-related characteristics.
FFQ data
Cohorts that assessed intake with FFQ data provided micronutrient data for ≥1 administration(s) (22% of participants had ≥2 FFQs). For cohorts (n = 3) that administered the FFQ and/or collected dietary supplement information multiple times in pregnancy, data were averaged for analysis. By design, FFQs provide estimates of usual daily intake over time and do not require further modeling to account for day-to-day variability. As with recall data, we first transformed the distributions with the Box-Cox parameter that optimized the normality of the residuals on a per-micronutrient basis. The resulting transformed data produced errors with a distribution more closely approximating normality. We then fit a general linear mixed model to the transformed data that included a random effect to account for the clustering of participants within ECHO cohorts. Again, participants were assumed to be exchangeable within cohort, and thus have equal variance and equal correlation within cohorts. We used the model-provided estimates of the quantiles of the distribution of usual daily intake to calculate the proportion of participants with intakes below the EAR, above the AI, and above the UL, both overall and stratified by the sociodemographic and weight-related characteristics. For cohorts with diet and supplement data from FFQs, we added the daily intakes to calculate the proportion with inadequate or excessive intake from food and dietary supplements, again overall and within designated strata.
Harmonization of recall and FFQ data
As distributions of intake derived from recall methods are known to vary from FFQ methods (33), combining them can produce incorrect estimates. To evaluate the validity of combining data across cohorts that administered recalls compared with FFQs, we examined heterogeneity with a hypothesis-testing approach by assessing the difference in mean intake for each micronutrient between methodologies using a Satterthwaite t test at a Bonferroni-corrected ɑ level of 0.05/19 = 0.0026. For all micronutrients, differences in mean daily intakes were statistically significant different between recall and FFQ data. Therefore, we did not combine data across dietary assessment methodology but present results separately.
Statistical analyses
We used Cochran-Mantel-Haenszel (CMH) tests to assess whether the proportion of participants at risk for inadequate or excessive intake significantly differed across sociodemographic and weight-related characteristics. Analyses were conducted separately for each dietary assessment methodology and separately for food compared with food and supplements. For several micronutrients and demographic subgroups, the proportion of participants with inadequate or excessive intake was close to zero; thus, asymptotic methods were not valid. We utilized a permutation-based method to assess statistically significant differences (34). For ordered variables, an exact CMH test was used; for the unordered variable of race/ethnicity, a Monte Carlo CMH test was used (35). For each methodology and demographic variable where at least 1 proportion was non-zero, we report the P value for a difference in proportions across groups. When all proportions were exactly zero (i.e., no participants at risk in any group), no P value is reported. We interpret statistical significance with a Bonferroni-corrected ɑ level of 0.05/19 micronutrients = 0.0026 for inadequate intake and 0.05/12 micronutrients = 0.0042 for excessive intake. Among statistically significant results, we considered a result relevant to public health when the proportion at risk differs by ≥10%.
Results
Cohort-level characteristics are presented in Table 1, and participant-level characteristics combined across all cohorts are presented in Table 2. Just over half of the participants were non-Hispanic White (57%) or had earned a 4-y college degree or higher (51%). Mean prepregnancy BMI was 26.3, and few (<10%) experienced pregnancy complications related to diabetes, hypertension, or pre-eclampsia. Mean gestational age at assessment was 23 wk (range: 5–40 wk). Among cohorts with dietary supplement data, >99% of participants reported dietary supplement use in pregnancy. Participant characteristics were similarly distributed between those completing recalls and FFQs.
TABLE 2.
All participants (n = 9801) | Recall participants (n = 1910) | FFQ participants (n = 7891) | ||||
---|---|---|---|---|---|---|
Mean or n | SD or % | Mean or n | SD or % | Mean or n | SD or % | |
Maternal age, y | 30.2 | (5.9) | 28.2 | (6.0) | 30.6 | (5.7) |
14–18 y | 182 | (2%) | 93 | (5%) | 89 | (1%) |
19–30 y | 4728 | (48%) | 1050 | (55%) | 3678 | (47%) |
31–50 y | 4786 | (49%) | 715 | (37%) | 4071 | (52%) |
Missing | 105 | (1%) | 52 | (3%) | 53 | (1%) |
Maternal race/ethnicity | ||||||
Hispanic, any race | 1830 | (19%) | 516 | (27%) | 1314 | (17%) |
Non-Hispanic White | 5442 | (56%) | 930 | (49%) | 4512 | (57%) |
Non-Hispanic Black | 1543 | (16%) | 290 | (15%) | 1253 | (16%) |
Non-Hispanic other | 718 | (7%) | 149 | (8%) | 569 | (7%) |
Missing | 268 | (3%) | 25 | (1%) | 243 | (3%) |
Maternal education | ||||||
<High school degree | 759 | (8%) | 263 | (14%) | 496 | (6%) |
High school diploma or GED | 1794 | (18%) | 400 | (21%) | 1394 | (18%) |
Some college or 2-y degree | 2197 | (22%) | 417 | (22%) | 1780 | (23%) |
4-y degree or more | 4969 | (51%) | 793 | (42%) | 4176 | (53%) |
Missing | 82 | (1%) | 37 | (2%) | 45 | (1%) |
Maternal prepregnancy BMI, kg/m2 | 26.3 | (6.4) | 26.2 | (6.5) | 26.3 | (6.4) |
Underweight (<18.5) | 342 | (3%) | 98 | (5%) | 244 | (3%) |
Normal (18.5–24.9) | 4777 | (49%) | 924 | (48%) | 3,853 | (49%) |
Overweight (25–29.9) | 2367 | (24%) | 460 | (24%) | 1907 | (24%) |
Obese (≥30) | 2212 | (23%) | 428 | (22%) | 1784 | (23%) |
Missing | 103 | (1%) | 0 | (0%) | 103 | (1%) |
Pregestational diabetes | 114 | (1%) | 8 | (0%) | 106 | (1%) |
Gestational diabetes | 614 | (6%) | 77 | (4%) | 537 | (7%) |
Pre-eclampsia or gestational hypertension | 879 | (9%) | 147 | (8%) | 732 | (9%) |
Prenatal smoking | 727 | (7%) | 151 | (8%) | 576 | (7%) |
Values are means (SDs) or n (%). For participants who reported prenatal dietary intake data retrospectively at 2–5 y after delivery (n = 508 FFQ participants), age and prepregnancy BMI in early pregnancy were obtained from medical records and education at the time of pregnancy was recalled retrospectively at 2–5 y after delivery. FFQ, food-frequency questionnaire; GED, graduate equivalency degree.
Risk of inadequate daily intake
The percentage of participants at risk of inadequate daily intake is presented in Supplemental Figure 1 (vitamins with and without dietary supplements), Supplemental Figure 2 (minerals with and without dietary supplements), Supplemental Table 1 (food intake only), and Supplemental Table 2 (food and dietary supplements), stratified by dietary assessment methodology. Regardless of methodology, approximately 1 in 5 participants or fewer were at risk of inadequate daily intake of riboflavin, niacin, vitamin B-12, and phosphorus, based on food sources alone, which decreased to very few participants (∼5% or fewer) when dietary supplement use was considered. Approximately one-quarter to one-third of participants were at risk of inadequate daily intake of vitamins A and C, thiamin, vitamin B-6, copper, calcium, and zinc from food sources alone, although estimates of inadequacy for vitamin C were notably higher when based on recall methods (49% vs. 20% for FFQ). Use of dietary supplements reduced the risk of inadequacy to ∼5% or less for vitamins A, C, and B-6, and zinc for both methodologies, and also for thiamin, calcium, and copper based on recall methodology. Risk of inadequacy remained at 10–20% for thiamin, calcium, and copper, even with dietary supplement use based on FFQ methods. Approximately half of participants were at risk of inadequate daily intake of folate and magnesium based on food intake alone, with higher risk for folate based on FFQ methods (59% vs. 41% for recall). Dietary supplement use greatly reduced risk for folate (down to 11% for FFQs, 0% for recalls) but not magnesium (∼40%). The majority of participants (>70%) were at risk of inadequate daily intake of vitamins E and D and iron based on food alone; with dietary supplements, up to 20% of participants remained at risk for inadequate vitamin E and iron intake, and up to 40% for inadequate vitamin D intake.
The percentage of participants with daily vitamin K intake exceeding the AI based on food alone was higher with FFQs (73%) than recalls (43%), but dietary supplement use resulted in the majority of participants exceeding the AI for both methods (75% and 63%, respectively). Less than half of participants had daily potassium intakes above the AI based on food alone (36–43%), which did not notably increase with dietary supplement use (37–53%).
Risk of excessive daily intake
The percentage of participants at risk of excessive daily intake is presented in Supplemental Figure 3 (with and without dietary supplements), Supplemental Table 1 (food intake only) and Supplemental Table 2 (food and dietary supplements), stratified by dietary assessment methodology. Regardless of methodology, almost no participants (≤5%) were at risk of excessive daily intake of any micronutrient based on foods alone. With dietary supplement use, risk of excessive daily intake was notable for folic acid (32% based on FFQ, 51% based on recall), iron (∼40%), and zinc (∼20%).
Disparities in risks
Risks of inadequate daily intake according to sociodemographic characteristics are presented in Table 3 (food intake only) and Table 4 (food and dietary supplements) for nutrients that were statistically significant and deemed relevant to public health. Full results are presented in Supplemental Tables 3–10, stratified by dietary assessment methodology.
TABLE 3.
n | % | n | % | n | % | n | % | n | % | P | |
24-Hour dietary recalls, n and % at risk | |||||||||||
Age disparities | Overall | 14–18 y | 19–30 y | 31–50 y | |||||||
% below EAR | |||||||||||
Vitamin A (μg/d) | 1910 | 42% | 93 | 53% | 1031 | 45% | 734 | 37% | — | — | <0.0012 |
Calcium (mg/d) | 1910 | 34% | 93 | 59% | 1031 | 36% | 734 | 30% | — | — | <0.0012 |
Copper (μg/d) | 1910 | 24% | 93 | 38% | 1031 | 27% | 734 | 18% | — | — | <0.0012 |
Magnesium (mg/d) | 1910 | 53% | 93 | 81% | 1031 | 57% | 734 | 47% | — | — | <0.0012 |
Phosphorus (mg/d) | 1910 | 6% | 93 | 40% | 1031 | 7% | 734 | 5% | — | — | <0.0012 |
% above AI | |||||||||||
Vitamin K (μg/d) | 1910 | 43% | 93 | 37% | 1031 | 39% | 734 | 50% | — | — | <0.0012 |
Racial/ethnic disparities | Overall | Hispanic | NH White | NH Black | Other | ||||||
% below EAR | |||||||||||
Vitamin A (μg/d) | 1910 | 42% | 516 | 49% | 930 | 33% | 290 | 50% | 149 | 46% | <0.0012 |
Vitamin E (mg/day) | 1910 | 73% | 516 | 80% | 930 | 68% | 290 | 76% | 149 | 73% | <0.0012 |
Vitamin B-6 (mg/d) | 1910 | 17% | 516 | 17% | 930 | 15% | 290 | 23% | 149 | 3% | <0.0012 |
Folate, B-9 (μg/d) | 1910 | 41% | 516 | 47% | 930 | 36% | 290 | 44% | 149 | 44% | <0.0012 |
Calcium (mg/d) | 1910 | 34% | 516 | 22% | 930 | 8% | 290 | 21% | 149 | 20% | <0.0012 |
Copper (μg/d) | 1910 | 24% | 516 | 32% | 930 | 18% | 290 | 31% | 149 | 23% | <0.0012 |
Magnesium (mg/d) | 1910 | 53% | 516 | 61% | 930 | 45% | 290 | 65% | 149 | 56% | <0.0012 |
Zinc (mg/d) | 1910 | 38% | 516 | 42% | 930 | 36% | 290 | 38% | 149 | 41% | 0.25 |
% above AI | |||||||||||
Vitamin K (μg/d) | 1910 | 43% | 516 | 34% | 930 | 50% | 290 | 37% | 149 | 43% | <0.0012 |
Potassium (mg/d) | 1909 | 36% | 516 | 35% | 930 | 42% | 289 | 31% | 149 | 37% | <0.0012 |
Educational disparities | Overall | <HS | HS or GED | Some college | ≥4 y degree | ||||||
% below EAR | |||||||||||
Vitamin A (μg/d) | 1910 | 42% | 263 | 53% | 400 | 47% | 417 | 43% | 793 | 32% | <0.0012 |
Vitamin E (mg/d) | 1910 | 73% | 263 | 80% | 400 | 78% | 417 | 76% | 793 | 64% | <0.0012 |
Riboflavin, B-2 (mg/d) | 1910 | 18% | 263 | 23% | 400 | 19% | 417 | 19% | 793 | 13% | <0.0012 |
Vitamin B-6 (mg/d) | 1910 | 17% | 263 | 24% | 400 | 16% | 417 | 18% | 793 | 14% | <0.0012 |
Calcium (mg/d) | 1910 | 34% | 263 | 22% | 400 | 9% | 417 | 19% | 793 | 9% | <0.0012 |
Copper (μg/d) | 1910 | 24% | 263 | 33% | 400 | 29% | 417 | 24% | 793 | 14% | <0.0012 |
Magnesium (mg/d) | 1910 | 53% | 263 | 66% | 400 | 61% | 417 | 57% | 793 | 38% | <0.0012 |
% above AI | |||||||||||
Vitamin K (μg/d) | 1910 | 43% | 263 | 31% | 400 | 36% | 417 | 39% | 793 | 56% | <0.0012 |
Potassium (mg/d) | 1909 | 36% | 263 | 24% | 399 | 22% | 417 | 33% | 793 | 46% | <0.0012 |
BMI disparities | Overall | Underweight | Normal | Overweight | Obese | ||||||
% below EAR | |||||||||||
Vitamin A (μg/d) | 1910 | 42% | 98 | 38% | 924 | 39% | 460 | 42% | 428 | 48% | <0.0012 |
Vitamin C (mg/d) | 1910 | 49% | 98 | 11% | 924 | 21% | 460 | 24% | 428 | 30% | <0.0012 |
Vitamin E (mg/d) | 1910 | 73% | 98 | 69% | 924 | 69% | 460 | 74% | 428 | 79% | <0.0012 |
Thiamin, B-1 (mg/d) | 1910 | 28% | 98 | 22% | 924 | 26% | 460 | 29% | 428 | 32% | <0.0012 |
Vitamin B-6 (mg/d) | 1910 | 17% | 98 | 3% | 924 | 15% | 460 | 19% | 428 | 22% | <0.0012 |
Folate, B-9 (μg/d) | 1910 | 41% | 98 | 32% | 924 | 39% | 460 | 43% | 428 | 46% | <0.0012 |
Magnesium (mg/d) | 1910 | 53% | 98 | 48% | 924 | 48% | 460 | 53% | 428 | 61% | <0.0012 |
% above AI | |||||||||||
Vitamin K (μg/d) | 1910 | 43% | 98 | 43% | 924 | 49% | 460 | 42% | 428 | 36% | <0.0012 |
Potassium (mg/d) | 1909 | 36% | 98 | 40% | 923 | 41% | 460 | 35% | 428 | 24% | <0.0012 |
Food-frequency questionnaires | |||||||||||
Age disparities | Overall | 14–18 y | 19–30 y | 31–50 y | |||||||
% below EAR | |||||||||||
Vitamin A (μg/d) | 7767 | 31% | 87 | 39% | 3315 | 34% | 4312 | 30% | — | — | 0.14 |
Calcium (mg/d) | 7891 | 38% | 89 | 51% | 3353 | 38% | 4396 | 39% | — | — | 0.17 |
Copper (μg/d) | 7891 | 16% | 89 | 16% | 3353 | 17% | 4396 | 15% | — | — | 0.69 |
Magnesium (mg/d) | 7891 | 47% | 89 | 63% | 3353 | 49% | 4396 | 49% | — | — | 0.10 |
Phosphorus (mg/d) | 7891 | 7% | 89 | 34% | 3353 | 7% | 4396 | 7% | — | — | <0.0012 |
% above AI | |||||||||||
Vitamin K (μg/d) | 7696 | 73% | 89 | 67% | 3315 | 68% | 4241 | 78% | — | — | 0.004 |
Racial/ethnic disparities | Overall | Hispanic | NH White | NH Black | Other | ||||||
% below EAR | |||||||||||
Vitamin A (μg/d) | 7767 | 31% | 1299 | 36% | 4462 | 29% | 1214 | 33% | 560 | 33% | 0.03 |
Vitamin E (mg/d) | 7891 | 69% | 1314 | 75% | 4512 | 66% | 1253 | 75% | 569 | 70% | <0.001 |
Vitamin B-6 (mg/d) | 7891 | 36% | 1314 | 38% | 4512 | 34% | 1253 | 41% | 569 | 39% | <0.001 |
Folate, B-9 (μg/d) | 7891 | 59% | 1314 | 60% | 4512 | 57% | 1253 | 64% | 569 | 59% | <0.001 |
Calcium (mg/d) | 7891 | 38% | 1314 | 38% | 4512 | 35% | 1253 | 45% | 569 | 44% | <0.0012 |
Copper (μg/d) | 7891 | 16% | 1314 | 17% | 4512 | 14% | 1253 | 19% | 569 | 15% | <0.001 |
Magnesium (mg/d) | 7891 | 47% | 1314 | 50% | 4512 | 44% | 1253 | 53% | 569 | 48% | <0.001 |
Zinc (mg/d) | 7581 | 37% | 1314 | 38% | 4512 | 34% | 943 | 44% | 569 | 40% | <0.0012 |
% above AI | |||||||||||
Vitamin K (μg/d) | 7696 | 73% | 1283 | 62% | 4397 | 77% | 1238 | 73% | 535 | 75% | <0.0012 |
Potassium (mg/d) | 7891 | 43% | 1314 | 43% | 4512 | 46% | 1253 | 37% | 569 | 38% | <0.001 |
Educational disparities | Overall | <HS | HS or GED | Some college | ≥4-y degree | ||||||
% below EAR | |||||||||||
Vitamin A (μg/d) | 7767 | 31% | 487 | 34% | 1379 | 33% | 1745 | 32% | 4119 | 30% | 0.14 |
Vitamin E (mg/d) | 7891 | 69% | 496 | 72% | 1394 | 73% | 1780 | 72% | 4176 | 67% | 0.001 |
Riboflavin, B-2 (mg/d) | 7891 | 18% | 496 | 16% | 1394 | 17% | 1780 | 18% | 4176 | 18% | 0.62 |
Vitamin B-6 (mg/d) | 7891 | 36% | 496 | 35% | 1394 | 36% | 1780 | 37% | 4176 | 36% | 0.93 |
Calcium (mg/d) | 7891 | 38% | 496 | 34% | 1394 | 37% | 1780 | 39% | 4176 | 39% | 0.40 |
Copper (μg/d) | 7891 | 16% | 496 | 14% | 1394 | 17% | 1780 | 17% | 4176 | 15% | 0.23 |
Magnesium (mg/d) | 7891 | 47% | 496 | 46% | 1394 | 48% | 1780 | 49% | 4176 | 46% | 0.24 |
% above AI | |||||||||||
Vitamin K (μg/d) | 7696 | 73% | 488 | 62% | 1379 | 67% | 1727 | 71% | 4059 | 78 | <0.0012 |
Potassium (mg/d) | 7891 | 43% | 496 | 49% | 1394 | 45% | 1780 | 42% | 4176 | 42 | 0.21 |
BMI disparities | Overall | Underweight | Normal | Overweight | Obese | ||||||
% below EAR | |||||||||||
Vitamin A (μg/d) | 7767 | 31% | 241 | 29% | 3782 | 30% | 1878 | 32% | 1766 | 34% | 0.05 |
Vitamin C (mg/d) | 7891 | 20% | 244 | 18% | 3853 | 20% | 1907 | 21% | 1784 | 21% | 0.56 |
Vitamin E (mg/d) | 7891 | 69% | 244 | 67% | 3853 | 67% | 1907 | 71% | 1784 | 73% | 0.02 |
Thiamin, B-1 (mg/d) | 7891 | 32% | 244 | 27% | 3853 | 30% | 1907 | 32% | 1784 | 34% | 0.03 |
Vitamin B-6 (mg/d) | 7891 | 36% | 244 | 35% | 3853 | 34% | 1907 | 37% | 1784 | 39% | 0.06 |
Folate, B-9 (μg/d) | 7891 | 59% | 244 | 56% | 3853 | 56% | 1907 | 60% | 1784 | 62% | <0.001 |
Magnesium (mg/d) | 7891 | 47% | 244 | 42% | 3853 | 44% | 1907 | 49% | 1784 | 50% | 0.06 |
% above AI | |||||||||||
Vitamin K (μg/d) | 7696 | 73% | 240 | 72% | 3770 | 76% | 1864 | 71% | 1724 | 71% | 0.40 |
Potassium (mg/d) | 7891 | 43% | 244 | 48% | 3853 | 44% | 1907 | 42% | 1784 | 42% | 0.39 |
AI, Adequate Intake; EAR, Estimated Average Requirement; ECHO, Environmental influences on Child Health Outcomes; GED, general education degree; HS, high school diploma; NH, non-Hispanic.
Statistical significance defined by Bonferroni-corrected ɑ level of 0.05/19 micronutrients = 0.0026 for inadequate intake. Among statistically significant results, we consider a result relevant to public health when the proportion at risk differs by ≥10%.
TABLE 4.
n | % | n | % | n | % | n | % | n | % | P | |
24-Hour dietary recalls, n and % at risk | |||||||||||
Age disparities | Overall | 14–18 y | 19–30 y | 31–50 y | |||||||
% below EAR | |||||||||||
Calcium (mg/d) | 1427 | 5% | 93 | 29% | 791 | 6% | 500 | 3% | — | — | <0.0012 |
Copper (μg/d) | 1427 | 6% | 93 | 17% | 791 | 6% | 500 | 3% | — | — | <0.0012 |
Magnesium (mg/d) | 1427 | 39% | 93 | 91% | 791 | 47% | 500 | 27% | — | — | <0.0012 |
Phosphorus (mg/d) | 1427 | 0% | 93 | 24% | 791 | 0% | 500 | 0% | — | — | <0.0012 |
% above AI | |||||||||||
Vitamin K (μg/d) | 1427 | 63% | 93 | 40% | 791 | 51% | 500 | 81% | — | — | <0.0012 |
Potassium (mg/d) | 1426 | 37% | 93 | 36% | 790 | 32% | 500 | 46% | — | — | <0.0012 |
Racial/ethnic disparities | Overall | Hispanic | NH White | NH Black | Other | ||||||
% below EAR | |||||||||||
Vitamin E (mg/d) | 1427 | 17% | 350 | 26% | 731 | 14% | 209 | 12% | 137 | 29% | <0.0012 |
Calcium (mg/d) | 1427 | 5% | 350 | 11% | 731 | 2% | 209 | 7% | 137 | 7% | <0.0012 |
Copper (μg/d) | 1427 | 6% | 350 | 12% | 731 | 3% | 209 | 5% | 137 | 9% | <0.0012 |
Magnesium (mg/d) | 1427 | 39% | 350 | 53% | 731 | 27% | 209 | 65% | 137 | 56% | <0.0012 |
% above AI | |||||||||||
Vitamin K (μg/d) | 1427 | 63% | 350 | 41% | 731 | 74% | 209 | 50% | 137 | 54% | <0.0012 |
Potassium (mg/d) | 1426 | 37% | 350 | 32% | 731 | 42% | 208 | 29% | 137 | 30% | <0.0012 |
Educational disparities | Overall | <HS | HS or GED | Some college | ≥4-y degree | ||||||
% below EAR | |||||||||||
Vitamin E (mg/d) | 1427 | 17% | 220 | 26% | 267 | 18% | 337 | 19% | 602 | 13% | <0.0012 |
Calcium (mg/d) | 1427 | 5% | 220 | 12% | 267 | 1% | 337 | 9% | 602 | 2% | <0.0012 |
Copper (μg/d) | 1427 | 6% | 220 | 13% | 267 | 6% | 337 | 7% | 602 | 2% | <0.0012 |
Magnesium (mg/d) | 1427 | 39% | 220 | 67% | 267 | 55% | 337 | 53% | 602 | 24% | <0.0012 |
Phosphorus (mg/d) | 1427 | 0% | 220 | 0% | 267 | 0% | 337 | 0% | 602 | 0% | — |
% above AI | |||||||||||
Vitamin K (μg/d) | 1427 | 63% | 220 | 26% | 267 | 38% | 337 | 47% | 602 | 83% | <0.0012 |
Potassium (mg/d) | 1426 | 37% | 220 | 25% | 266 | 24% | 337 | 34% | 602 | 46% | <0.0012 |
BMI disparities | Overall | Underweight | Normal weight | Overweight | Obese | ||||||
% below EAR | |||||||||||
Magnesium (mg/d) | 1427 | 39% | 51 | 32% | 731 | 34% | 351 | 47% | 294 | 57% | <0.0012 |
% above AI | |||||||||||
Vitamin K (μg/d) | 1427 | 63% | 51 | 54% | 731 | 71% | 351 | 57% | 294 | 43% | <0.0012 |
Potassium (mg/d) | 1426 | 37% | 51 | 53% | 730 | 40% | 351 | 35% | 294 | 27% | <0.0012 |
Food-frequency questionnaires | |||||||||||
Age disparities | Overall | 14–18 y | 19–30 y | 31–50 y | |||||||
% below EAR | |||||||||||
Calcium (mg/d) | 5606 | 22% | 87 | 37% | 2403 | 23% | 3065 | 22% | — | — | 0.05 |
Copper (μg/d) | 4731 | 20% | 85 | 21% | 2134 | 21% | 2461 | 18% | — | — | 0.49 |
Magnesium (mg/d) | 4731 | 41% | 85 | 57% | 2134 | 42% | 2461 | 41% | — | — | 0.04 |
Phosphorus (mg/d) | 1872 | 1% | 14 | 44% | 443 | 2% | 1415 | 1% | — | — | <0.0012 |
% above AI | |||||||||||
Vitamin K (μg/d) | 2532 | 75% | 18 | 62% | 710 | 69% | 1804 | 79% | — | — | <0.0012 |
Potassium (mg/d) | 2532 | 53% | 18 | 59% | 710 | 50% | 1804 | 54% | — | — | 0.16 |
Racial/ethnic disparities | Overall | Hispanic | NH White | NH Black | Other | ||||||
% below EAR | |||||||||||
Vitamin E (mg/d) | 5609 | 22% | 895 | 29% | 2991 | 18% | 1194 | 25% | 363 | 22% | <0.0012 |
Calcium (mg/d) | 5606 | 22% | 895 | 22% | 2990 | 19% | 1193 | 26% | 362 | 25% | <0.001 |
Copper (μg/d) | 4731 | 20% | 717 | 23% | 2479 | 18% | 1143 | 21% | 226 | 18% | 0.07 |
Magnesium (mg/d) | 4731 | 41% | 717 | 43% | 2479 | 36% | 1143 | 45% | 226 | 41% | <0.001 |
% above AI | |||||||||||
Vitamin K (μg/d) | 2532 | 75% | 446 | 64% | 1546 | 78% | 289 | 77% | 183 | 81% | 0.03 |
Potassium (mg/d) | 2532 | 53% | 446 | 56% | 1546 | 53% | 289 | 46% | 183 | 48% | 0.03 |
Educational disparities | Overall | <HS | HS or GED | Some college | ≥4-y degree | ||||||
% below EAR | |||||||||||
Vitamin E (mg/d) | 5609 | 22% | 462 | 29% | 1164 | 25% | 1172 | 24% | 2779 | 18% | <0.0012 |
Calcium (mg/d) | 5606 | 22% | 462 | 22% | 1164 | 23% | 1170 | 23% | 2778 | 22% | 0.61 |
Copper (μg/d) | 4731 | 20% | 426 | 22% | 1079 | 21% | 874 | 21% | 2322 | 18% | 0.14 |
Magnesium (mg/d) | 4731 | 41% | 426 | 41% | 1079 | 41% | 874 | 43% | 2322 | 40% | 0.56 |
Phosphorus (mg/d) | 1872 | 1% | 41 | 27% | 146 | 6% | 406 | 2% | 1271 | 1% | <0.0012 |
% above AI | |||||||||||
Vitamin K (μg/d) | 2532 | 75% | 114 | 62% | 260 | 62% | 514 | 72% | 1621 | 80% | <0.0012 |
Potassium (mg/d) | 2532 | 53% | 114 | 58% | 260 | 50% | 514 | 51% | 1621 | 53% | 0.77 |
BMI disparities | Overall | Underweight | Normal weight | Overweight | Obese | ||||||
% below EAR | |||||||||||
Magnesium (mg/d) | 4731 | 41% | 174 | 35% | 2406 | 39% | 1082 | 44% | 1037 | 43% | 0.62 |
% above AI | |||||||||||
Vitamin K (μg/d) | 2532 | 75% | 88 | 76% | 1465 | 78% | 573 | 71% | 399 | 71% | 0.41 |
Potassium (mg/d) | 2532 | 53% | 88 | 51% | 1465 | 54% | 573 | 50% | 399 | 52% | 0.74 |
AI, Adequate Intake; EAR, Estimated Average Requirement; ECHO, Environmental influences on Child Health Outcomes; GED, general education degree; HS, high school diploma; NH, non-Hispanic.
Statistical significance defined by Bonferroni-corrected ɑ level of 0.05/19 micronutrients = 0.0026 for inadequate intake. Among statistically significant results, we consider a result relevant to public health when the proportion at risk differs by ≥10%.
Age
For both assessment methodologies, more younger participants (14–18 y) had intakes below the EAR for phosphorus and above the AI for vitamin K from food alone (Supplemental Table 3) and with dietary supplements (Supplemental Table 4). Similar age-related disparities were also evident for vitamin A, calcium, copper, magnesium, and potassium with recall methods only. Risks of excessive daily intake did not differ by age for any nutrient with either methodology.
Race/ethnicity
The risk of not meeting the EAR or AI on food alone varied by race/ethnicity for vitamins A, E, and B-6, folate, calcium, copper, magnesium, vitamin K, and potassium based on recall methods, and for calcium, zinc, and vitamin K based on FFQ methods (Supplemental Table 5). Regardless of methodology, non-Hispanic White participants were at the lowest risk of inadequate intakes. When nutrients from dietary supplements were considered (Supplemental Table 6), disparities persisted for vitamin E with both methods, with non-Hispanic White and Black participants at lowest risk. Disparities also persisted with recall methods for calcium, copper, magnesium, vitamin K, and potassium with recall methods, again with non-Hispanic White participants at the lowest risk of inadequate intake. Disparities in risks of excessive daily intake were evident from recall methods only for folic acid (P = 0.003), with non-Hispanic Black (57%) and White (53%) participants having higher risks for excessive intake than Hispanic (43%) or other race/ethnicity (47%) participants.
Education
The risk of inadequacy based on food only varied by education for vitamins A and E, riboflavin, vitamin B-6, calcium, copper, and magnesium using recall data only, with college-educated participants having the lowest risks (Supplemental Table 7). Similarly, more participants with 4-y degrees exceeded the AI for vitamin K using both assessment methods and potassium with recalls only. When nutrients from dietary supplements were considered (Supplemental Table 8), participants without a high school education were at disparately higher risk for inadequate daily intake for vitamin E based on both methods; for calcium, copper, and magnesium based on recalls only; and for phosphorus based on FFQs only. A greater percentage of participants having at least some college education exceeded the AI for vitamin K (both methods) and potassium (recalls only). Risk of excessive daily intake did not vary by education for any nutrient with either methodology.
Prepregnancy BMI
Risks of inadequate daily intake varied by prepregnancy BMI for vitamins A, C, and E, thiamin, vitamin B-6, folate, and magnesium based on recall methods; no disparities in risks were evident based on FFQ methods (Supplemental Table 9). Participants with obesity were at highest risk of inadequate daily intake of these nutrients, followed by participants with overweight. Fewer participants with obesity, and with overweight to a lesser degree, exceeded the AI for vitamin K and potassium. These weight-related disparities persisted with dietary supplements only for magnesium, vitamin K, and potassium. Risk of excessive daily intake did not vary by prepregnancy BMI for any nutrient with either methodology.
Discussion
In this diverse sample of nearly 10,000 pregnant females across the United States, we report substantial risk of inadequacy for multiple nutrients from food alone, underscoring the need to improve diet quality of pregnant females and use dietary supplements when appropriate. Particularly at risk for inadequate daily intake were participants who were aged 14–18 y, identified as Hispanic, Black, or other races/ethnicities (i.e., not non-Hispanic White), had less than a high school education, or had overweight or obesity before pregnancy. Dietary supplement use attenuated all disparities in risks for inadequate intakes of vitamins A and C, thiamin, riboflavin, vitamin B-6, folate, and zinc, and the BMI disparities for vitamin E. However, disparities in risks of inadequate intake by at least 1 sociodemographic or weight-related characteristic persisted even with dietary supplements for vitamin E, calcium, copper, magnesium, phosphorus, vitamin K, and potassium. This work highlights the variability in how well dietary supplements address the gap between food-based micronutrient daily intake and DRIs for pregnant females. As our results mirror intake disparities evident in nonpregnant adults (36–38), pregnancy may be an important opportunity to address persistent gaps in nutrient intake given increased contact with providers and often heightened attention to their diet and health.
Very few participants in our study (<5%) were at risk of excessive daily intake for any micronutrient based on food alone, but this increased with dietary supplement use, most notably for iron (∼40%), folic acid (>30%), and zinc (∼20%), similar to a recent NHANES analysis (10). A U-shaped relation between iron and reproductive outcomes has been previously reported, with excessive daily intake associated with increased risk of low birth weight, small-for-gestational age neonates, and (inconsistently) gestational diabetes (39). Excessive folic acid intake is concerning as animal studies indicate high intakes may increase offspring cardiometabolic risks through altered DNA methylation (40, 41), and emerging human studies affirm that maternal folic acid intake may affect offspring DNA methylation (42, 43). While effects of epigenetic shifts on offspring outcomes are not well understood, our results emphasize the urgency of understanding the impact of widespread excessive folic acid intake. This is especially important for females of non-Hispanic Black race/ethnicity, who were at the highest risk of excessive daily intake of folic acid with dietary supplement use and already experience disparities in obesity, diabetes, and cardiovascular diseases (44–46).
Importantly, disparities in risks of inadequate daily intake remained with dietary supplement use, albeit much reduced compared with food alone, suggesting personalized approaches for dietary counseling and dietary supplement recommendations are needed. Yet, this would be challenging for busy clinicians who are not equipped to assess prenatal dietary intake and provide individualized advice (47). While registered dietitian nutritionists could assess intake and provide personalized recommendations to pregnant women, availability and reimbursement for such services varies [only 50% of states reimburse these services for Medicaid beneficiaries (48)]. For both clinical counseling and public health messaging, it would be beneficial to identify key food groups to increase and the specific dietary supplements best formulated to address common micronutrient shortfalls without inducing excess intake. Improved diet during pregnancy has been difficult to achieve (49), particularly very early in pregnancy, a critical period of fetal development; therefore, increased efforts to improve maternal micronutrient intake prior to pregnancy are critical.
The implications of having ≥1 of 5 females at risk of inadequate daily intake of vitamins D, E, and K, choline, magnesium, and potassium alone or in combination in terms of offspring health are relatively unknown. Magnesium supplementation of up to 400 mg/d in generally healthy pregnant females has not consistently affected blood pressure, pre-eclampsia, intrauterine growth restriction, or preterm delivery (50–52); however, baseline magnesium intake was not reported in these studies, so it is unclear if intake was low without supplementation (50–52), and blood concentrations of magnesium did not differ between groups post-treatment (50). There is emerging evidence that choline supplementation to achieve daily intakes of 480 to >900 mg/d (well above the AI of 450 mg/d) may benefit offspring cognitive and behavioral outcomes (53, 54), which may be highly relevant given that <25% of our participants exceeded the AI for choline. As most dietary supplements in the United States contain very little choline (10, 55), increased consumption of choline-rich food (eggs, other protein sources) (56) in pregnancy is needed to address the relatively low intakes. Vitamins K and E and potassium have been so understudied in relation to pregnancy outcomes that the DRIs for these nutrients are based on needs for nonpregnant females (57–59). Further research is needed to evaluate whether the disparities in micronutrient intake observed here contribute to adverse pregnancy outcomes or intergenerational inequalities in health risks and chronic disease.
Our overall results align with a recent report of intake among pregnant women in the United States estimated from 2001–2014 NHANES data (10), even though enrollment into ECHO was not designed to be nationally representative. Our sample was 10-fold larger than the NHANES sample and included data collected over a similar period (1999–2019 vs. 2001–2014) following mandatory folic acid fortification of enriched cereal grain products (60). Racial/ethnic distributions in both studies were similar. Relatively more ECHO participants had earned 4-y college degrees (51% vs. 29%), which likely reflects the willingness of more highly educated individuals to enroll in health research studies (61, 62). Nonetheless, results were similar for food-based nutrient analyses. Differences between the studies are more evident for dietary supplement analyses; risks of inadequate intake were notably lower in ECHO for vitamins A, C, D, E, and B-6; folate; vitamin K; and iron; and risks for excessive intake were higher for folic acid, iron, and zinc. These differences are likely driven by the higher prevalence of dietary supplement use in ECHO (>99%) than in the US population of pregnant women (70%), resulting in more of our participants consuming higher levels of these nutrients. Yet, given the similarity in participant characteristics and risks of inadequate or excessive intake, the ECHO consortium is well positioned to provide nationally relevant data from a large sample of pregnant participants on prenatal micronutrient intake and subsequent effects on offspring outcomes. Moreover, our study extends the NHANES analysis by highlighting subgroups at disparately higher risk of inadequate or excessive micronutrient intake in pregnancy, an analysis that requires a large, diverse sample.
Limitations of our study include potential underreporting (63) of intake for all methods and analysis of FFQ data given that recalls are preferred for evaluating proportions above/below thresholds (27), especially given evidence that FFQs may overestimate micronutrient intake relative to recalls (64) and biomarker recovery studies (65). There was notable heterogeneity in the FFQs utilized; however, all were validated previously (19–25, 64). Variability in nutrient estimates across databases could have contributed to error in our estimates, especially when supplement data were estimated with mean nutrient values for each type of supplement rather than brand/type. Despite the use of different methodologies and nutrient databases across cohorts and over time, food-based results were similar between methodologies (±10%) for most nutrients, including directionality in disparity analyses (even though statistical significance was not similarly reached). Results with dietary supplements varied more between methodologies, but sample sizes varied across analyses and direct comparisons should be interpreted with caution. We had data from relatively fewer participants aged 14–18 y, with other races/ethnicities (i.e., not Hispanic, White, or Black), or underweight BMI, especially in dietary supplement analyses, which limits the interpretation of findings for these subgroups. Some disparity in findings may be due to type 1 error arising from multiple comparisons, even with adjusted thresholds for interpretation. One cohort retrospectively assessed prenatal diet at 2–5 y postpartum, which may be subject to more recall error and actually represent the postpartum diet more than prenatal diet; however, prior studies have shown that dietary intake changes little from pregnancy to postpartum (66, 67). We also did not consider clustering of inadequate or excessive intakes across micronutrients or subpopulations, which could be informative for targeted efforts to improve comprehensive intake. Analysis of differences by trimester or over time was beyond the scope of this paper, but should be examined by future studies. Last, we did not consider bioavailability or solubility of micronutrients from fortified food and dietary supplements, which has implications for downstream effects on maternal/child outcomes. We note that there is often a discrepancy between population prevalence of nutritional risk when dietary intakes are used compared with when biomarkers are used (68). This is complicated further by our focus on pregnancy because reference ranges for nutritional biomarkers in this state can differ from nonpregnancy because of hemodilution and other changes that occur during pregnancy (69). The ECHO consortium is well positioned to conduct futures studies of circulating biomarkers in pregnancy, and thereby address knowledge gaps about associations with reported intake and maternal/offspring health outcomes.
In summary, our study highlights suboptimal daily intake of multiple micronutrients during pregnancy in the United States, and notable disparities in risks of inadequate intake even with dietary supplement use according to age, race/ethnicity, education, and prepregnancy BMI. While it is important to clarify how suboptimal daily intake of micronutrients in pregnancy impacts offspring health outcomes, clinicians serving younger or minority pregnant females with obesity or less education should particularly attend to nutritional needs now, including discussion of dietary habits and use of dietary supplements. Increased consumption of foods rich in nutrients commonly underconsumed is critical. Reformulation of prenatal dietary supplements may also be needed to address these shortfalls while reducing excessive intakes of folic acid, iron, and zinc.
Supplementary Material
Acknowledgments
The authors acknowledge the contribution of the following ECHO program collaborators—ECHO Components–Coordinating Center: Duke Clinical Research Institute, Durham, NC: PB Smith, KL Newby, DK Benjamin; Data Analysis Center: Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD: LP Jacobson; Research Triangle Institute, Durham, NC: CB Parker. The authors’ responsibilities were as follows—ALD, AJE, MMH, LAA, CVB, IH-P, MRK, DM, RJS, TGO, ESB, SSC, JMK, LT, FAT, RJW, SK, and DD: designed the cohort-level research; ALD, EPF, AJE, DCM, YZ, CVB, RJS, TGO, ESB, KMS, LT, and FAT: conducted the research; KAS, PMG, RLB, DJC, BMR, DHG, and DD: designed the pooled research question and analysis; KAS, RNH, BMR, ALD, EPF, DCM, YZ, JH, KL, RJS, SSC, LT, FAT, RJW, and SK: prepared and provided cohort-level data for the pooled analysis; RNH, BMR, and DHG: conducted the pooled analysis; KAS, RH, BMR, and DHG: wrote the manuscript; KAS: had primary responsibility for final content; and all authors: read and approved the final manuscript.
Notes
Research reported in this publication was supported by the Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health, under award numbers U2COD023375 (Coordinating Center), U24OD023382 (Data Analysis Center), U24OD023319 (PRO Core), and UG3/UH3OD023248, R01DK076648, UL1TR00108, R01GM121081, U01CA215834, UG3/UH3OD02325, P42ES017198, UG3/UH3OD023318, R01NR014800, K01NR017664, UG3/UH3OD023279, U01HD045935, UG3/UH3OD023289, K01DK120807, UG3/UH3OD023287, P50ES026086, UG3/UH3OD023365, R01ES031701, UG3/UH3OD023275, P42ES007373, P01ES022832, UO1TS000135, UG3/UH3OD023344, UG3/UH3OD023342, R01ES016443, UG3/UH3OD023365, R24ES028533, R01ES031701, UG3/UH3OD023349, R01HD034568, R01HD096032, UG3/UH3OD023286, UG3/UH3OD023285, UG3/UH3OD023305, R01HL132338-01A1, UG3/UH3OD023271, R01HL109977, UG3/UH3OD023337, R01HL095606, R01HD082078, R21ES021318, K01HL141589, U24OD023382, K01HL141589, the Environmental Protection Agency (83615801-0, RD-83544201), and Autism Speaks (AS5938).
Author disclosures: Unrelated to this submission, RLB has served as a consultant in the past to the NIH Office of Dietary Supplements, Nestle/Gerber, the General Mills Bell Institute, RTI International, and Nutrition Impact; RLB is a trustee of the International Food Information Council and a board member of the International Life Sciences Institute–North America. In the past she has received travel support to present her research on dietary supplements. RLB is an editor on the Journal of Nutrition and played no role in the Journal's evaluation of the manuscript. The other authors report no conflicts of interest. The sponsors had no role in in the study design; collection, analysis, and interpretation of data; writing of the report; or the decision to submit the report for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Supplemental Figures 1–3 and Supplemental Tables 1–10 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents available on https://academic.oup.com/jn/.
See the Acknowledgments for a full listing of ECHO collaborators.
Abbreviations used: AI, Adequate Intake; CMH, Cochran-Mantel-Haenszel; EAR, Estimated Average Requirement; ECHO, Environmental influences on Child Health Outcomes; FFQ, food-frequency questionnaire; UL, Tolerable Upper Intake Level.
Contributor Information
Katherine A Sauder, Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Robyn N Harte, Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Brandy M Ringham, Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Patricia M Guenther, Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA.
Regan L Bailey, Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.
Akram Alshawabkeh, College of Engineering, Northeastern University, Boston, MA, USA.
José F Cordero, Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, GA, USA.
Anne L Dunlop, Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA.
Erin P Ferranti, Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA.
Amy J Elliott, Avera Research Institute, Sioux Falls, SD, USA.
Diane C Mitchell, Department of Nutritional Sciences, Penn State University, University Park, PA, USA.
Monique M Hedderson, Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Lyndsay A Avalos, Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Yeyi Zhu, Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Carrie V Breton, Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Leda Chatzi, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Jin Ran, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Irva Hertz-Picciotto, Department of Public Health Sciences, School of Medicine, University of California, Davis, Davis, CA, USA.
Margaret R Karagas, Department of Epidemiology, Dartmouth College, Hanover, NH, USA.
Vicki Sayarath, Department of Epidemiology, Dartmouth College, Hanover, NH, USA.
Joseph Hoover, Community Environmental Health Program, College of Pharmacy at the University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Debra MacKenzie, Community Environmental Health Program, College of Pharmacy at the University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Kristen Lyall, AJ Drexel Autism Institute, Drexel University, Philadelphia, PA, USA.
Rebecca J Schmidt, Department of Public Health Sciences, School of Medicine, University of California, Davis, Davis, CA, USA.
Thomas G O'Connor, Departments of Psychiatry, Psychology, Neuroscience, and Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY, USA.
Emily S Barrett, Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA.
Karen M Switkowski, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Sarah S Comstock, Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA.
Jean M Kerver, Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA.
Leonardo Trasande, Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA.
Frances A Tylavsky, Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
Rosalind J Wright, Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Srimathi Kannan, Department of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, USA.
Noel T Mueller, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Diane J Catellier, RTI International, Research Triangle Park, NC, USA.
Deborah H Glueck, Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Dana Dabelea, Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Program Collaborators for Environmental influences on Child Health Outcomes (ECHO):
P B Smith, K L Newby, D K Benjamin, L P Jacobson, and C B Parker
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